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  • 1. Afset, J. E.
    et al.
    Larssen, K. W.
    Bergh, K.
    Larkeryd, A.
    Sjodin, A.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Forsman, M.
    Phylogeographical pattern of Francisella tularensis in a nationwide outbreak of tularaemia in Norway, 20112015In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 20, no 19, p. 9-14, article id 21125Article in journal (Refereed)
    Abstract [en]

    In 2011, a nationwide outbreak of tularaemia occurred in Norway with 180 recorded cases. It was associated with the largest peak in lemming density seen in 40 years. Francisella tularensis was isolated from 18 patients. To study the geographical distribution of F. tularensis genotypes in Norway and correlate genotype with epidemiology and clinical presentation, we performed whole genome sequencing of patient isolates. All 18 genomes from the outbreak carried genetic signatures of F. tularensis subsp. holarctica and were assigned to genetic clades using canonical single nucleotide polymorphisms. Ten isolates were assigned to major genetic clade B.6 (subclade B.7), seven to clade B.12, and one to clade B.4. The B.6 subclade B.7 was most common in southern and central Norway, while clade B.12 was evenly distributed between the southern, central and northern parts of the country. There was no association between genotype and clinical presentation of tularaemia, time of year or specimen type. We found extensive sequence similarity with F. tularensis subsp. holarctica genomes from high-endemic tularaemia areas in Sweden. Finding nearly identical genomes across large geographical distances in Norway and Sweden imply a life cycle of the bacterium without replication between the outbreaks and raise new questions about long-range migration mechanisms.

  • 2. Ahlinder, Jon
    et al.
    Ohrman, Caroline
    Svensson, Kerstin
    Lindgren, Petter
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Forsman, Mats
    Larsson, Pär
    Sjödin, Andreas
    Increased knowledge of Francisella genus diversity highlights the benefits of optimised DNA-based assays2012In: BMC Microbiology, E-ISSN 1471-2180, Vol. 12, p. 220-Article in journal (Refereed)
    Abstract [en]

    Background: Recent advances in sequencing technologies offer promising tools for generating large numbers of genomes, larger typing databases and improved mapping of environmental bacterial diversity. However, DNA-based methods for the detection of Francisella were developed with limited knowledge about genetic diversity. This, together with the high sequence identity between several Francisella species, means there is a high risk of false identification and detection of the highly virulent pathogen Francisella tularensis. Moreover, phylogenetic reconstructions using single or limited numbers of marker sequences often result in incorrect tree topologies and inferred evolutionary distances. The recent growth in publicly accessible whole-genome sequences now allows evaluation of published genetic markers to determine optimal combinations of markers that minimise both time and laboratory costs. Results: In the present study, we evaluated 38 previously published DNA markers and the corresponding PCR primers against 42 genomes representing the currently known diversity of the genus Francisella. The results highlight that PCR assays for Francisella tularensis are often complicated by low specificity, resulting in a high probability of false positives. A method to select a set of one to seven markers for obtaining optimal phylogenetic resolution or diagnostic accuracy is presented. Conclusions: Current multiple-locus sequence-typing systems and detection assays of Francisella, could be improved by redesigning some of the primers and reselecting typing markers. The use of only a few optimally selected sequence-typing markers allows construction of phylogenetic topologies with almost the same accuracy as topologies based on whole-genome sequences.

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  • 3.
    Angelin, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Forsell, Joakim
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Granlund, Margareta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Evengård, Birgitta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Palmgren, Helena
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Risk factors for colonization with extended-spectrum beta-lactamase producing Enterobacteriaceae in healthcare students on clinical assignment abroad: A prospective study2015In: Travel Medicine and Infectious Disease, ISSN 1477-8939, E-ISSN 1873-0442, Vol. 13, no 3, p. 223-229Article in journal (Refereed)
    Abstract [en]

    Background: The increase of antibiotic resistance in clinically important bacteria is a worldwide threat, especially in healthcare environments. International travel is a risk factor for gut colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). The risk for healthcare students of being colonized with ESBL-PE when participating in patient-related work abroad has not been previously investigated. Methods: Swedish healthcare students travelling for pre-clinical and clinical courses outside Scandinavia submitted faecal samples and survey data before and after travel. The faecal samples were screened for ESBL-PE and carbapenemase-producing Enterobacteriaceae (CPE). Screening results and survey data were analysed to identify risk factors for colonization. Results: In the 99 subjects who submitted a full set of samples, 35% were colonized with a new ESBL-PE strain during travel. No CPE was found. The most important risk factor for ESBL-PE colonization was travel destination, and the highest colonization rate was found in the South East Asia region. Antibiotic treatment during travel was an independent risk factor for ESBL-PE colonization but patient-related work was not significantly associated with an increased risk. Conclusions: Patient-related work abroad was not a risk factor for ESBL-PE suggesting that transmission from patients is uncommon. Pre-travel advice on avoiding unnecessary antibiotic treatment during travel is recommended.

  • 4.
    Antti, Henrik
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Fahlgren, Anna
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Näsström, Elin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Kouremenos, Konstantinos
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Sundén-Cullberg, Jonas
    Guo, Yongzhi
    Moritz, Thomas
    Wolf-Watz, Hans
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Fällman, Maria
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Metabolic profiling for detection of staphylococcus aureus infection and antibiotic resistance2013In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 2, article id e56971Article in journal (Refereed)
    Abstract [en]

    Due to slow diagnostics, physicians must optimize antibiotic therapies based on clinical evaluation of patients without specific information on causative bacteria. We have investigated metabolomic analysis of blood for the detection of acute bacterial infection and early differentiation between ineffective and effective antibiotic treatment. A vital and timely therapeutic difficulty was thereby addressed: the ability to rapidly detect treatment failures because of antibiotic-resistant bacteria. Methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) were used and for infecting mice, while natural MSSA infection was studied in humans. Samples of bacterial growth media, the blood of infected mice and of humans were analyzed with combined Gas Chromatography/Mass Spectrometry. Multivariate data analysis was used to reveal the metabolic profiles of infection and the responses to different antibiotic treatments. experiments resulted in the detection of 256 putative metabolites and mice infection experiments resulted in the detection of 474 putative metabolites. Importantly, ineffective and effective antibiotic treatments were differentiated already two hours after treatment start in both experimental systems. That is, the ineffective treatment of MRSA using cloxacillin and untreated controls produced one metabolic profile while all effective treatment combinations using cloxacillin or vancomycin for MSSA or MRSA produced another profile. For further evaluation of the concept, blood samples of humans admitted to intensive care with severe sepsis were analyzed. One hundred thirty-three putative metabolites differentiated severe MSSA sepsis (n = 6) from severe sepsis (n = 10) and identified treatment responses over time. Combined analysis of human, , and mice samples identified 25 metabolites indicative of effective treatment of sepsis. Taken together, this study provides a proof of concept of the utility of analyzing metabolite patterns in blood for early differentiation between ineffective and effective antibiotic treatment in acute infections.

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  • 5. Ariza-Miguel, Jaime
    et al.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Fernández-Natal, María Isabel
    Martínez-Nistal, Carmen
    Orduña, Antonio
    Rodríguez-Ferri, Elías F
    Hernández, Marta
    Rodríguez-Lázaro, David
    Molecular investigation of tularemia outbreaks, Spain, 1997-20082014In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 20, no 5, p. 754-761Article in journal (Refereed)
    Abstract [en]

    Tularemia outbreaks occurred in northwestern Spain in 1997-1998 and 2007-2008 and affected >1,000 persons. We assessed isolates involved in these outbreaks by using pulsed-field gel electrophoresis with 2 restriction enzymes and multilocus variable number tandem repeat analysis of 16 genomic loci of Francisella tularensis, the cause of this disease. Isolates were divided into 3 pulsotypes by pulsed-field gel electrophoresis and 8 allelic profiles by multilocus variable number tandem repeat analysis. Isolates obtained from the second tularemia outbreak had the same genotypes as isolates obtained from the first outbreak. Both outbreaks were caused by genotypes of genetic subclade B.Br:FTNF002-00, which is widely distributed in countries in central and western Europe. Thus, reemergence of tularemia in Spain was not caused by the reintroduction of exotic strains, but probably by persistence of local reservoirs of infection.

  • 6. Bengtsson-Palme, Johan
    et al.
    Angelin, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Huss, Mikael
    Kjellqvist, Sanela
    Kristiansson, Erik
    Palmgren, Helena
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Larsson, D. G. Joakim
    Johansson, Anders
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    The Human Gut Microbiome as a Transporter of Antibiotic Resistance Genes between Continents2015In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 59, no 10, p. 6551-6560Article in journal (Refereed)
    Abstract [en]

    Previous studies of antibiotic resistance dissemination by travel have, by targeting only a select number of cultivable bacterial species, omitted most of the human microbiome. Here, we used explorative shotgun metagenomic sequencing to address the abundance of >300 antibiotic resistance genes in fecal specimens from 35 Swedish students taken before and after exchange programs on the Indian peninsula or in Central Africa. All specimens were additionally cultured for extended-spectrum beta-lactamase (ESBL)-producing enterobacteria, and the isolates obtained were genome sequenced. The overall taxonomic diversity and composition of the gut microbiome remained stable before and after travel, but there was an increasing abundance of Proteobacteria in 25/35 students. The relative abundance of antibiotic resistance genes increased, most prominently for genes encoding resistance to sulfonamide (2.6-fold increase), trimethoprim (7.7-fold), and beta-lactams (2.6-fold). Importantly, the increase observed occurred without any antibiotic intake. Of 18 students visiting the Indian peninsula, 12 acquired ESBL-producing Escherichia coli, while none returning from Africa were positive. Despite deep sequencing efforts, the sensitivity of metagenomics was not sufficient to detect acquisition of the low-abundant genes responsible for the observed ESBL phenotype. In conclusion, metagenomic sequencing of the intestinal microbiome of Swedish students returning from exchange programs in Central Africa or the Indian peninsula showed increased abundance of genes encoding resistance to widely used antibiotics.

  • 7. Birdsell, D. N.
    et al.
    Özsürekci, Y.
    Rawat, A.
    Aycan, A. E.
    Mitchell, C. L.
    Sahl, J. W.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Colman, R. E.
    Schupp, J. M.
    Ceyhan, M.
    Keim, P. S.
    Wagner, D. M.
    Coinfections identified from metagenomic analysis of cervical lymph nodes from tularemia patients2018In: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 18, article id 319Article in journal (Refereed)
    Abstract [en]

    Background: Underlying coinfections may complicate infectious disease states but commonly go unnoticed because an a priori clinical suspicion is usually required so they can be detected via targeted diagnostic tools. Shotgun metagenomics is a broad diagnostic tool that can be useful for identifying multiple microbes simultaneously especially if coupled with lymph node aspirates, a clinical matrix known to house disparate pathogens. The objective of this study was to analyze the utility of this unconventional diagnostic approach (shotgun metagenomics) using clinical samples from human tularemia cases as a test model. Tularemia, caused by the bacterium Francisella tularensis, is an emerging infectious disease in Turkey. This disease commonly manifests as swelling of the lymph nodes nearest to the entry of infection. Because swollen cervical nodes are observed from many different types of human infections we used these clinical sample types to analyze the utility of shotgun metagenomics.

    Methods: We conducted an unbiased molecular survey using shotgun metagenomics sequencing of DNA extracts from fine-needle aspirates of neck lymph nodes from eight tularemia patients who displayed protracted symptoms. The resulting metagenomics data were searched for microbial sequences (bacterial and viral).

    Results: F. tularensis sequences were detected in all samples. In addition, we detected DNA of other known pathogens in three patients. Both Hepatitis B virus (HBV) and Human Parvovirus B-19 were detected in one individual and Human Parvovirus B-19 alone was detected in two other individuals. Subsequent PCR coupled with Sanger sequencing verified the metagenomics results. The HBV status was independently confirmed via serological diagnostics, despite evading notice during the initial assessment.

    Conclusion: Our data highlight that shotgun metagenomics of fine-needle lymph node aspirates is a promising clinical diagnostic strategy to identify coinfections. Given the feasibility of the diagnostic approach demonstrated here, further steps to promote integration of this type of diagnostic capability into mainstream clinical practice are warranted.

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  • 8. Birdsell, Dawn N
    et al.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Öhrman, Caroline
    Swedish Defense Research Agency, Umeå.
    Kaufman, Emily
    Molins, Claudia
    Pearson, Talima
    Gyuranecz, Miklós
    Naumann, Amber
    Vogler, Amy J
    Myrtennäs, Kerstin
    Swedish Defense Research Agency, Umeå.
    Larsson, Pär
    Swedish Defense Research Agency, Umeå.
    Forsman, Mats
    Swedish Defense Research Agency, Umeå.
    Sjödin, Andreas
    Swedish Defense Research Agency, Umeå.
    Gillece, John D
    Schupp, James
    Petersen, Jeannine M
    Keim, Paul
    Wagner, David M
    Francisella tularensis subsp. tularensis group A.I, United States2014In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 20, no 5, p. 861-865Article in journal (Refereed)
    Abstract [en]

    We used whole-genome analysis and subsequent characterization of geographically diverse strains using new genetic signatures to identify distinct subgroups within Francisella tularensis subsp. tularensis group A.I: A.I.3, A.I.8, and A.I.12. These subgroups exhibit complex phylogeographic patterns within North America. The widest distribution was observed for A.I.12, which suggests an adaptive advantage.

  • 9. Birgand, G.
    et al.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Szilagyi, E.
    Lucet, J. -C
    Overcoming the obstacles of implementing infection prevention and control guidelines2015In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 21, no 12, p. 1067-1071Article, review/survey (Refereed)
    Abstract [en]

    Reasons for a successful or unsuccessful implementation of infection prevention and control (IPC) guidelines are often multiple and interconnected. This article reviews key elements from the national to the individual level that contribute to the success of the implementation of IPC measures and gives perspectives for improvement. Governance approaches, modes of communication and formats of guidelines are discussed with a view to improve collaboration and transparency among actors. The culture of IPC influences practices and varies according to countries, specialties and healthcare providers. We describe important contextual aspects, such as relationships between actors and resources and behavioural features including professional background or experience. Behaviour change techniques providing goal-setting, feedback and action planning have proved effective in mobilizing participants and may be key to trigger social movements of implementation. The leadership of international societies in coordinating actions at international, national and institutional levels using multidisciplinary approaches and fostering collaboration among clinical microbiology, infectious diseases and IPC will be essential for success. Clinical Microbiology and Infection (C) 2015 European Society of Clinical Microbiology and Infectious Diseases. 

  • 10.
    Blom, Kim
    et al.
    Public Health Agency of Sweden, Sweden.
    Fjällström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Molnár, Christian
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Familjeläkarna AB, Stockholm, Sweden.
    Åberg, Mikael
    Department of Medical Sciences, Clinical Chemistry and SciLifeLab Affinity Proteomics, Uppsala University, Uppsala, Sweden.
    Vikström, Linnea
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Wigren, Julia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Bennet, Louise
    Clinical Studies Sweden, Forum South, Skåne University Hospital and Department of Clinical Sciences, Lund University, Lund, Sweden.
    Widerström, Micael
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Rasmussen, Gunlög
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Klingström, Jonas
    Department of Biomedical Clinical Sciences, Linköping University, Linköping, Sweden.
    Forsell, Mattias N. E.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    SARS-CoV-2-related mortality decrease in nursing home residents given multiple COVID-19 boosters2023In: The Lancet - Infectious diseases, ISSN 1473-3099, E-ISSN 1474-4457, Vol. 23, no 10, p. e393-e394Article in journal (Other academic)
  • 11. Bonnedahl, J
    et al.
    Drobni, P
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Hernandez, J
    Melhus, A
    Stedt, J
    Olsen, B
    Drobni, M
    Characterization, and comparison, of human clinical and black-headed gull (Larus ridibundus) extended-spectrum beta-lactamase-producing bacterial isolates from Kalmar, on the southeast coast of Sweden2010In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 65, no 9, p. 1939-1944Article in journal (Refereed)
    Abstract [en]

    The finding of CTX-M-type ESBLs in E. coli isolated from black-headed gulls in Sweden, where 'background resistance' is low, is consistent with an ongoing environmental spread of these plasmid-borne resistance genes. The results indicate that a potential for transfer between the human population and environment exists even in countries with a low level of antibiotic resistance.

  • 12. Bonnedahl, Jonas
    et al.
    Drobni, Mirva
    Gauthier-Clerc, Michel
    Hernandez, Jorge
    Granholm, Susanne
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Kayser, Yves
    Melhus, Asa
    Kahlmeter, Gunnar
    Waldenström, Jonas
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Olsen, Björn
    Uppsala universitet.
    Dissemination of Escherichia coli with CTX-M type ESBL between humans and yellow-legged gulls in the south of France2009In: PLOS ONE, E-ISSN 1932-6203, Vol. 4, no 6, p. e5958-Article in journal (Refereed)
    Abstract [en]

    Extended Spectrum beta-Lactamase (ESBL) producing Enterobacteriaceae started to appear in the 1980s, and have since emerged as some of the most significant hospital-acquired infections with Escherichia coli and Klebsiella being main players. More than 100 different ESBL types have been described, the most widespread being the CTX-M beta-lactamase enzymes (bla(CTX-M) genes). This study focuses on the zoonotic dissemination of ESBL bacteria, mainly CTX-M type, in the southern coastal region of France. We found that the level of general antibiotic resistance in single randomly selected E. coli isolates from wild Yellow-legged Gulls in France was high. Nearly half the isolates (47.1%) carried resistance to one or more antibiotics (in a panel of six antibiotics), and resistance to tetracycline, ampicillin and streptomycin was most widespread. In an ESBL selective screen, 9.4% of the gulls carried ESBL producing bacteria and notably, 6% of the gulls carried bacteria harboring CTX-M-1 group of ESBL enzymes, a recently introduced and yet the most common clinical CTX-M group in France. Multi locus sequence type and phylogenetic group designations were established for the ESBL isolates, revealing that birds and humans share E. coli populations. Several ESBL producing E. coli isolated from birds were identical to or clustered with isolates with human origin. Hence, wild birds pick up E. coli of human origin, and with human resistance traits, and may accordingly also act as an environmental reservoir and melting pot of bacterial resistance with a potential to re-infect human populations.

  • 13.
    Brundin, Peik
    et al.
    S:t Görans Sjukhus, Infektionsenheten.
    Landgren, Britt-Marie
    Kvinnohälsan, Karolinska University Hospital.
    Fjällström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Gustafsson, Jan-Åke
    Department of Biosciences and Nutrition, Karolinska Institutet.
    Johansson, Anders F.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Nalvarte, Ivan
    Department of Biosciences and Nutrition, Karolinska Institutet.
    Expression of sex hormone receptor and immune response genes in peripheral blood mononuclear cells during the menstrual cycleManuscript (preprint) (Other academic)
  • 14.
    Brundin, Peik M.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden; Unit of Infectious Diseases, Department of Medicine, St Göran’s Hospital, Stockholm, Sweden.
    Landgren, Britt-Marie
    Karolinska University Hospital, Huddinge, Sweden.
    Fjällström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Shamekh, Mohamed M.
    Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden; Department of Biochemistry, Faculty of Veterinary Medicine, Assiut University, Assiut, Egypt.
    Gustafsson, Jan-Åke
    Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden; Center for Nuclear Receptors and Cell Signaling, University of Houston, TX, Houston, United States.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Nalvarte, Ivan
    Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
    Expression of Sex Hormone Receptor and Immune Response Genes in Peripheral Blood Mononuclear Cells During the Menstrual Cycle2021In: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 12, article id 721813Article in journal (Refereed)
    Abstract [en]

    Sex hormones are known to interact with the immune system on multiple levels but information on the types of sex hormone receptors (SHR) and their expression levels in immune cells is scarce. Estrogen, testosterone and progesterone are all considered to interact with the immune system through their respective cell receptors (ERα and ERβ including the splice variant ERβ2, AR and PGR). In this study expression levels of SHR genes in peripheral blood mononuclear cells (PBMCs) and cell subsets (CD4+ and CD8+ T-cells, CD56+ NK-cells, CD14+ monocytes and CD19+ B-cells) were analyzed using standard manual qPCR or a qPCR array (TLDA). Nine healthy individuals including men (n = 2), premenopausal (Pre-MP, n = 5) and postmenopausal (post-MP, n = 2) women were sampled for PBMCs which were separated to cell subsets using FACS. Ten Pre-MP women were longitudinally sampled for total PBMCs at different phases of the menstrual cycle. We found that ERα was most abundant and, unexpectedly, that ERβ2 was the dominant ERβ variant in several FACS sorted cell subsets. In total PBMCs, SHR (ERα, ERβ1, ERβ2, and AR) expression did not fluctuate according to the phase of the menstrual cycle and PGR was not expressed. However, several immune response genes (GATA3, IFNG, IL1B, LTA, NFKB1, PDCD1, STAT3, STAT5A, TBX21, TGFB1, TNFA) were more expressed during the ovulatory and mid-luteal phases. Sex hormone levels did not correlate significantly with gene expression of SHR or immune response genes, but sex hormone-binding globulin (SHBG), a steroid hormone transporting protein, was positively correlated to expression of ERβ1 gene. This study provides new insights in the distribution of ERs in immune cells. Furthermore, expression patterns of several immune response genes differ significantly between phases of the menstrual cycle, supporting a role for sex hormones in the immune response.

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  • 15.
    Brundin, Peik M.A.
    et al.
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden; S:t Görans Hospital, Dept of Medicine, Unit of Infectious Diseases, Stockholm, Sweden.
    Landgren, Britt-Marie
    Fjällström, Peter
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Johansson, Anders F.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Nalvarte, Ivan
    Blood hormones and torque teno virus in peripheral blood mononuclear cells2020In: Heliyon, E-ISSN 2405-8440, Vol. 6, no 11, article id e05535Article in journal (Refereed)
    Abstract [en]

    Men and women respond differently to infectious diseases. Women show less morbidity and mortality, partially due to the differences in sex hormone levels which can influence the immune response. Torque teno virus (TTV) is non-pathogenic and ubiquitously present in serum from a large proportion (up to 90%) of adult humans with virus levels correlating with the status of the host immune response. The source of TTV replication is unknown, but T-lymphocytes have been proposed. In this study we investigated the presence and levels of TTV in peripheral blood mononuclear cells (PBMCs) in premenopausal (pre-MP) women, post-menopausal (post-MP) women, and men, and determined their serum sex hormone levels. Of the examined subjects (n = 27), we found presence of TTV in PMBC from 17.6% pre-MP (n = 17), 25.0% post-MP (n = 4) and 50.0% men (n = 6). The levels of TTV/μg DNA were lower among TTV-positive men and post-MP women compared to pre-MP women. All the positive pre-MP women were either anovulatory, hypothyroid, or both. In addition, the TTV-positive pre-MP women had significantly lower progesterone levels compared to TTV-negative pre-MP women. Although our study was performed on a limited number of subjects, the data suggests that TTV in PBMC is associated with an anovulatory menstrual cycle with low progesterone levels, and possibly with male sex.

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  • 16. Byström, Mona
    et al.
    Böcher, Sidsel
    Magnusson, Anna
    Umeå University, Faculty of Medicine, Clinical Microbiology, Infectious Diseases.
    Prag, Jørgen
    Johansson, Anders
    Umeå University, Faculty of Medicine, Clinical Microbiology, Infectious Diseases.
    Tularemia in Denmark: identification of a Francisella tularensis subsp. holarctica strain by real-time PCR and high-resolution typing by multiple-locus variable-number tandem repeat analysis.2005In: Journal of Clinical Microbiology, ISSN 0095-1137, Vol. 43, no 10, p. 5355-8Article in journal (Refereed)
    Abstract [en]

    We report ulceroglandular tularemia affecting an 8-year-old boy and the first recovery of Francisella tularensis in Denmark. A novel real-time PCR assay was used to identify the strain as F. tularensis subsp. holarctica (type B). Multiple-locus variable-number tandem repeat analysis demonstrated a close genetic relationship to strains from Norway.

  • 17.
    Carrara, Elena
    et al.
    Division of Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, Italy; European Committee on Infection Control (EUCIC), Basel, Switzerland.
    Ong, David S.Y.
    Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands; ESCMID Study Group for Respiratory Viruses (ESGREV), Basel, Switzerland.
    Hussein, Khetam
    European Committee on Infection Control (EUCIC), Basel, Switzerland; The Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Infection Control Unit, Rambam Health Care Campus, Haifa, Israel.
    Keske, Siran
    European Committee on Infection Control (EUCIC), Basel, Switzerland; Department of Infectious Diseases and Clinical Microbiology, Koç University School of Medicine, Istanbul, Turkey.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). European Committee on Infection Control (EUCIC), Basel, Switzerland.
    Presterl, Elisabeth
    European Committee on Infection Control (EUCIC), Basel, Switzerland; Department of Infection Control and Hospital Epidemiology, Medical University of Vienna, Vienna, Austria.
    Tsioutis, Constantinos
    European Committee on Infection Control (EUCIC), Basel, Switzerland; School of Medicine, European University Cyprus, Nicosia, Cyprus.
    Tschudin-Sutter, Sarah
    Division of Infectious Diseases & Hospital Epidemiology, University Hospital Basel and University of Basel, Basel, Switzerland.
    Tacconelli, Evelina
    Division of Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, Italy; European Committee on Infection Control (EUCIC), Basel, Switzerland.
    ESCMID guidelines on testing for SARS-CoV-2 in asymptomatic individuals to prevent transmission in the health care setting2022In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 28, no 5, p. 672-680Article in journal (Refereed)
    Abstract [en]

    Scope: This guideline addresses the indications for direct testing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic individuals in health care facilities, with the aim to prevent SARS-CoV-2 transmissions in these settings. The benefit of testing asymptomatic individuals to create a safe environment for patients and health care workers must be weighed against potential unintended consequences, including delaying necessary treatments owing to false positive results and lower quality of care owing to strict isolation measures.

    Methods: A total of nine PICOs (population, intervention, comparison, outcome) on the topic of testing asymptomatic individuals was selected by the panel members. Subsequently, a literature search for existing guidelines and systematic reviews was performed on PubMed, Epistemonikos, and RecMap using relevant filters available in each database. Data on article/recommendation type, setting, target population, intervention, and quality of the evidence were extracted. Credibility of the systematic reviews was evaluated using the AMSTAR tool, and level of agreement with available recommendation was evaluated with the AGREE II score. Because the evidence available from systematic reviews was deemed insufficiently updated to formulate relevant recommendations, an additional search targeting relevant guidance documents from major public health institutions and original studies was performed. Provisional recommendations were discussed via web conferences until agreement was reached, and final recommendations were formulated according to the GRADE approach.

    Recommendations: Recommendations were formulated regarding systematic testing in asymptomatic individuals upon admission to a health care setting, during hospital stay, before elective procedures, and before scheduled nonsurgical procedures. Moreover, recommendations regarding testing of asymptomatic visitors, personal caregivers, and health care workers in health care facilities were presented. Recommendations also were given on contact tracing in asymptomatic patients or health care workers and the possibility of a negative screening test to shorten the quarantine period. Furthermore, if applicable, recommendations were specified to transmission rate and vaccination coverage.

  • 18.
    Dave, Nishi
    et al.
    Department of Medicine, Division of Infectious Diseases, Karolinska Institutet, Stockholm, Solna, Sweden.
    Sjöholm, Daniel
    Department of Medicine, Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden.
    Hedberg, Pontus
    Department of Medicine, Division of Infectious Diseases, Karolinska Institutet, Stockholm, Solna, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
    Ternhag, Anders
    Department of Medicine, Division of Infectious Diseases, Karolinska Institutet, Stockholm, Solna, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
    Granath, Fredrik
    Department of Medicine, Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden.
    Verberk, Janneke D M
    Department of Medical Microbiology and Infection Prevention, University Medical Centre Utrecht, Utrecht, Netherlands; Department of Epidemiology, Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, Netherlands.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    van der Werff, Suzanne D.
    Department of Medicine, Division of Infectious Diseases, Karolinska Institutet, Stockholm, Solna, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
    Nauclér, Pontus
    Department of Medicine, Division of Infectious Diseases, Karolinska Institutet, Stockholm, Solna, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
    Nosocomial SARS-CoV-2 infections and mortality during unique COVID-19 epidemic waves2023In: JAMA Network Open, E-ISSN 2574-3805, Vol. 6, no 11, article id e2341936Article in journal (Refereed)
    Abstract [en]

    Importance: Quantifying the burden of nosocomial SARS-CoV-2 infections and associated mortality is necessary to assess the need for infection prevention and control measures.

    Objective: To investigate the occurrence of nosocomial SARS-CoV-2 infections and associated 30-day mortality among patients admitted to hospitals in Region Stockholm, Sweden.

    Design, Setting, and Participants: A retrospective, matched cohort study divided the period from March 1, 2020, until September 15, 2022, into a prevaccination period, early vaccination and pre-Omicron (period 1), and late vaccination and Omicron (period 2). From among 303 898 patients 18 years or older living in Region Stockholm, 538 951 hospital admissions across all hospitals were included. Hospitalized admissions with nosocomial SARS-CoV-2 infections were matched to as many as 5 hospitalized admissions without nosocomial SARS-CoV-2 by age, sex, length of stay, admission time, and hospital unit.

    Exposure: Nosocomial SARS-CoV-2 infection defined as the first positive polymerase chain reaction test result at least 8 days after hospital admission or within 2 days after discharge.

    Main Outcomes and Measures: Primary outcome of 30-day mortality was analyzed using time-to-event analyses with a Cox proportional hazards regression model adjusted for age, sex, educational level, and comorbidities.

    Results: Among 2193 patients with SARS-CoV-2 infections or reinfections (1107 women [50.5%]; median age, 80 [IQR, 71-87] years), 2203 nosocomial SARS-CoV-2 infections were identified. The incidence rate of nosocomial SARS-CoV-2 infections was 1.57 (95% CI, 1.51-1.64) per 1000 patient-days. In the matched cohort, 1487 hospital admissions with nosocomial SARS-CoV-2 infections were matched to 5044 hospital admissions without nosocomial SARS-CoV-2 infections. Thirty-day mortality was higher in the prevaccination period (adjusted hazard ratio [AHR], 2.97 [95% CI, 2.50-3.53]) compared with period 1 (AHR, 2.08 [95% CI, 1.50-2.88]) or period 2 (AHR, 1.22 [95% CI, 0.92-1.60]). Among patients with nosocomial SARS-CoV-2 infections, 30-day AHR comparing those with 2 or more doses of SARS-CoV-2 vaccination and those with less than 2 doses was 0.64 (95% CI, 0.46-0.88).

    Conclusions and Relevance: In this matched cohort study, nosocomial SARS-CoV-2 infections were associated with higher 30-day mortality during the early phases of the pandemic and lower mortality during the Omicron variant wave and after the introduction of vaccinations. Mitigation of excess mortality risk from nosocomial transmission should be a strong focus when population immunity is low through implementation of adequate infection prevention and control measures.

  • 19.
    Desvars, Amélie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Furberg, Maria
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Hjertqvist, Marika
    Vidman, Linda
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Sjöstedt, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Rydén, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Epidemiology and Ecology of Tularemia in Sweden2015In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 44, p. 58-58Article in journal (Other academic)
  • 20.
    Desvars, Amélie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Furberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Hjertqvist, Marika
    Vidman, Linda
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Sjöstedt, Anders
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Rydén, Patrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Epidemiology and Ecology of Tularemia in Sweden, 1984-20122015In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 21, no 1, p. 32-39Article in journal (Refereed)
    Abstract [en]

    The zoonotic disease tularemia is endemic in large areas of the Northern Hemisphere, but research is lacking on patterns of spatial distribution and connections with ecologic factors. To describe the spatial epidemiology of and identify ecologic risk factors for tularemia incidence in Sweden, we analyzed surveillance data collected over 29 years (1984-2012). A total of 4,830 cases were notified, of which 3,524 met all study inclusion criteria. From the first to the second half of the study period, mean incidence increased 10-fold, from 0.26/100,000 persons during 1984-1998 to 2.47/100,000 persons during 1999 2012 (p<0.001). The incidence of tularemia was higher than expected in the boreal and alpine ecologic regions (p<0.001), and incidence was positively correlated with the presence of lakes and rivers (p<0.001). These results provide a comprehensive epidemiologic description of tularemia in Sweden and illustrate that incidence is higher in locations near lakes and rivers.

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  • 21.
    Dwibedi, Chinmay Kumar
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Division of CBRN Security and Defence, Swedish Defense Research Agency, Umeå, Sweden.
    Birdsell, Dawn
    Larkeryd, Adrian
    Myrtennas, Kerstin
    Ohrman, Caroline
    Nilsson, Elin
    Karlsson, Edvin
    Hochhalter, Christian
    Rivera, Andrew
    Maltinsky, Sara
    Bayer, Brittany
    Keim, Paul
    Scholz, Holger C.
    Tomaso, Herbert
    Wittwer, Matthias
    Beuret, Christian
    Schuerch, Nadia
    Pilo, Paola
    Hernandez Perez, Marta
    Rodriguez-Lazaro, David
    Escudero, Raquel
    Anda, Pedro
    Forsman, Mats
    Wagner, David M.
    Larsson, Par
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Long-range dispersal moved Francisella tularensis into Western Europe from the East2016In: Microbial Genomics, E-ISSN 2057-5858, Vol. 2, no 12Article in journal (Refereed)
    Abstract [en]

    For many infections transmitting to humans from reservoirs in nature, disease dispersal patterns over space and time are largely unknown. Here, a reversed genomics approach helped us understand disease dispersal and yielded insight into evolution and biological properties of Francisella tularensis, the bacterium causing tularemia. We whole-genome sequenced 67 strains and characterized by single-nucleotide polymorphism assays 138 strains, collected from individuals infected 1947-2012 across Western Europe. We used the data for phylogenetic, population genetic and geographical network analyses. All strains (n= 205) belonged to a monophyletic population of recent ancestry not found outside Western Europe. Most strains (n= 195) throughout the study area were assigned to a star-like phylogenetic pattern indicating that colonization of Western Europe occurred via clonal expansion. In the East of the study area, strains were more diverse, consistent with a founder population spreading from east to west. The relationship of genetic and geographic distance within the F. tularensis population was complex and indicated multiple long-distance dispersal events. Mutation rate estimates based on year of isolation indicated null rates; in outbreak hotspots only, there was a rate of 0.4 mutations/genome/year. Patterns of nucleotide substitution showed marked AT mutational bias suggestive of genetic drift. These results demonstrate that tularemia has moved from east to west in Europe and that F. tularensis has a biology characterized by long-range geographical dispersal events and mostly slow, but variable, replication rates. The results indicate that mutation-driven evolution, a resting survival phase, genetic drift and long-distance geographical dispersal events have interacted to generate genetic diversity within this species.

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  • 22.
    Dwibedi, Chinmay Kumar
    et al.
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Swedish Defense Research Agency, Umeå, Sweden.
    Larsson, Pär
    Swedish Defense Research Agency, Umeå, Sweden.
    Ahlinder, Jon
    Swedish Defense Research Agency, Umeå, Sweden.
    Lindgren, Petter
    Swedish Defense Research Agency, Umeå, Sweden.
    Myrtennäs, Kerstin
    Swedish Defense Research Agency, Umeå, Sweden.
    Granberg, Malin
    Swedish Defense Research Agency, Umeå, Sweden.
    Larsson, Eva
    Swedish Defense Research Agency, Umeå, Sweden.
    Öhrman, Caroline
    Swedish Defense Research Agency, Umeå, Sweden.
    Sjödin, Andreas
    Swedish Defense Research Agency, Umeå, Sweden.
    Stenberg, Per
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Swedish Defense Research Agency, Umeå, Sweden.
    Forsman, Mats
    Swedish Defense Research Agency, Umeå, Sweden.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Biological amplification of low frequency mutations unravels laboratory culture history of the bio-threat agent Francisella tularensis2020In: Forensic Science International: Genetics, ISSN 1872-4973, E-ISSN 1878-0326, Vol. 45Article in journal (Refereed)
    Abstract [en]

    Challenges of investigating a suspected bio attack include establishing if microorganisms have been cultured to produce attack material and to identify their source. Addressing both issues, we have investigated genetic variations that emerge during laboratory culturing of the bacterial pathogen Francisella tularensis. Key aims were to identify genetic variations that are characteristic of laboratory culturing and explore the possibility of using biological amplification to identify genetic variation present at exceedingly low frequencies in a source sample. We used parallel serial passage experiments and high-throughput sequencing of F. tularensis to explore the genetic variation. We found that during early laboratory culture passages of F. tularensis, gene duplications emerged in the pathogen genome followed by single-nucleotide polymorphisms in genes for bacterial capsule synthesis. Based on a biological enrichment scheme and the use of high-throughput sequencing, we identified genetic variation that likely pre-existed in a source sample. The results support that capsule synthesis gene mutations are common during laboratory culture, and that a biological amplification strategy is useful for linking a F. tularensis sample to a specific laboratory variant among many highly similar variants.

  • 23. Ecke, Frauke
    et al.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Forsman, Mats
    Khalil, Hussein
    Magnusson, Magnus
    Hörnfeldt, Birger
    Selective Predation by Owls on Infected Bank Voles (Myodes glareolus) as a Possible Sentinel of Tularemia Outbreaks2020In: Vector Borne and Zoonotic Diseases, ISSN 1530-3667, E-ISSN 1557-7759, Vol. 20, no 8, p. 630-632Article in journal (Refereed)
    Abstract [en]

    Tularemia is a widely spread zoonotic disease in the northern hemisphere, caused by the bacterium Francisella tularensis. In humans, tularemia is an acute febrile illness with incidence peaks in late summer to early autumn of outbreak years, but there is no early warning system in place that can reduce the impact of disease by providing timely risk information. In this study, we revisit previously unpublished data on F. tularensis in water, sediment, soil, and small mammals from 1984 in northern Sweden. In addition, we used human case data from the national surveillance system for tularemia in the same year. In the environmental and small mammal material, bank vole (Myodes glareolus) samples from urine and bladder were the only samples that tested positive for F. tularensis. The prevalence of F. tularensis among trapped bank voles was 13.5%, although all six bank voles that were retrieved from owl nest boxes in early May tested positive. Forty-two human tularemia cases were reported from August to December in 1984. Based on these results, we encourage investigating the potential role of tularemia-infected bank voles retrieved from owl nest boxes in spring as an early warning for outbreaks of tularemia among humans in summer and autumn of the same year.

  • 24.
    Edin, Alicia
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Granholm, Susanne
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Koskiniemi, Satu
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Allard, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Sjöstedt, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Development and Laboratory Evaluation of a Real-Time PCR Assay for Detecting Viruses and Bacteria of Relevance for Community-Acquired Pneumonia2015In: Journal of Molecular Diagnostics, ISSN 1525-1578, E-ISSN 1943-7811, Vol. 17, no 3, p. 315-324Article in journal (Refereed)
    Abstract [en]

    Community-acquired pneumonia may present with similar clinical symptoms, regardless of viral or bacterial cause. Diagnostic assays are needed to rapidly discriminate between causes, because this will guide decisions on appropriate treatment. Therefore, a quantitative real-time PCR (qPCR) assay with duplex reactions targeting eight bacteria and six viruses was developed. Technical performance was examined with linear plasmids. Upper and Lower respiratory tract specimens were used to compare the qPCR assay with standard microbiological methods. The limit of detection was 5 to 20 DNA template copies with approximately 1000-fold differences in concentrations of the two competing templates. SDs for positive controls were <5%. The use of the qPCR assay resulted in 113 positive identifications in 94 respiratory specimens compared with 38 by using standard diagnostics. Diagnostic accuracy of the qPCR assay varied between 60% positive agreement with standard tests for Streptococcus pneumoniae and 100% for Mycoplasma pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus. Negative percentage of agreement was >95% for M. pneumoniae, Streptococcus pyogenes, respiratory syncytial virus, and influenza A virus; whereas it was only 56% for Haemophilus influenzae. Multiple microbial agents were identified in 19 of 44 sputum and 19 of 50 nasopharynx specimens. We conclude that in parallel qPCR detection of the targeted respiratory bacteria and viruses is feasible. The results indicate good technical performance of the assay in clinical specimens.

  • 25.
    Ehyaie, Azadeh
    et al.
    Patientområde Infektion, Karolinska Universitetssjukhuset - Stockholm, Sweden Patientområde Infektion, Karolinska Universitetssjukhuset - Stockholm, Sweden, Sweden.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Aufwerber, Ewa
    Patientområde Infektion, Karolinska Universitetssjukhuset - Stockholm, Sweden Patientområde Infektion, Karolinska Universitetssjukhuset - Stockholm, Sweden, Sweden.
    Frej, Anna
    Patientområde Gastro, hud och reuma, Karolinska Universitetssjukhuset - Stockholm, Sweden Patientområde Gastro, hud och reuma, Karolinska Universitetssjukhuset - Stockholm, Sweden, Sweden.
    Eneslätt, Monica
    Region Västerbotten - Umeå, Sweden.
    Lindberg, Lena
    Region Västerbotten - Umeå, Sweden.
    Nauclér, Pontus
    Karolinska Universitetssjukhuset - Infektion Stockholm, Sweden Karolinska Universitetssjukhuset - Infektion Stockholm, Sweden, Sweden.
    Prevalensen av vårdrelaterade infektioner högre i svensk mätning:  Omgranskning av journaler gav bättre överensstämmelse mellan svensk punktprevalensmätning och ECDC-definitioner: [Prevalence of healthcare-associated infections based on Swedish point-prevalence survey compared to usage of the European Center of Disease Prevention and Control (ECDC) definitions]2020In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 117, no 4Article in journal (Refereed)
    Abstract [en]

    The purpose was to compare the prevalence of healthcare-associated infections (HAI) in the Swedish point prevalence survey with an assessment using the European Centre of Disease Prevention and Control (ECDC) definitions of HAI. A total of 1247 patients were included from three Swedish hospitals. The prevalence of HAI was higher in the Swedish survey as compared to when using the ECDC definitions. The correspondence between results according to Swedish and ECDC protocols was better in Region Västerbotten than at Karolinska University Hospital. In Västerbotten, but not at Karolinska University Hospital, quality control was performed on collected data in the Swedish point prevalence survey. The study highlights the importance of expert knowledge of HAI and quality control to obtain valid survey results.

  • 26.
    Esmaeili, Saber
    et al.
    National Reference laboratory for Plague, Tularemia and Q fever, Research Centre for Emerging and Reemerging infectious diseases, Pasteur Institute of Iran, Akanlu, Hamadan, Kabudar Ahang, Iran; Department of Epidemiology and Biostatistics, Research Centre for Emerging and Reemerging infectious diseases, Pasteur Institute of Iran, Tehran, Iran.
    Rohani, Mahdi
    National Reference laboratory for Plague, Tularemia and Q fever, Research Centre for Emerging and Reemerging infectious diseases, Pasteur Institute of Iran, Akanlu, Hamadan, Kabudar Ahang, Iran; Department of Microbiology, Pasteur Institute of Iran, Tehran, Iran.
    Ghasemi, Ahmad
    National Reference laboratory for Plague, Tularemia and Q fever, Research Centre for Emerging and Reemerging infectious diseases, Pasteur Institute of Iran, Akanlu, Hamadan, Kabudar Ahang, Iran; Department of Epidemiology and Biostatistics, Research Centre for Emerging and Reemerging infectious diseases, Pasteur Institute of Iran, Tehran, Iran; Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
    Gouya, Mohammad Mehdi
    Center for Communicable Disease Control, Ministry of Health and Medical Education, Tehran, Iran.
    Khayatzadeh, Simin
    Department of Communicable Disease Control, Deputy of Health, Tabriz University of Medical Sciences, Tabriz, Iran.
    Mahmoudi, Ahmad
    Department of Biology, Faculty of Science, Urmia University, Urmia, Iran.
    Ahangari Cohan, Hossein
    National Reference laboratory for Plague, Tularemia and Q fever, Research Centre for Emerging and Reemerging infectious diseases, Pasteur Institute of Iran, Akanlu, Hamadan, Kabudar Ahang, Iran; Department of Epidemiology and Biostatistics, Research Centre for Emerging and Reemerging infectious diseases, Pasteur Institute of Iran, Tehran, Iran.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Maurin, Max
    Universite Grenoble Alpes, CNRS, Grenoble INP, CHU Grenoble Alpes, TIMC-IMAG, 38000 Grenoble, Grenoble, France.
    Mostafavi, Ehsan
    National Reference laboratory for Plague, Tularemia and Q fever, Research Centre for Emerging and Reemerging infectious diseases, Pasteur Institute of Iran, Akanlu, Hamadan, Kabudar Ahang, Iran; Department of Epidemiology and Biostatistics, Research Centre for Emerging and Reemerging infectious diseases, Pasteur Institute of Iran, Tehran, Iran.
    Francisella tularensis human infections in a village of northwest Iran2021In: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 21, no 1, article id 310Article in journal (Refereed)
    Abstract [en]

    Background: Recent seroepidemiological studies have suggested that tularemia could be an endemic bacterial zoonosis in Iran.

    Methods: From January 2016 to June 2018, disease cases characterized by fever, cervical lymphadenopathy and ocular involvement were reported in Youzband Village of Kaleybar County, in the East Azerbaijan Province, northwestern Iran. Diagnostic tests included Francisella tularensis serology (including tube agglutination test and ELISA), PCR, and culture.

    Results: Among 11 examined case-patients, the tularemia tube agglutination test was positive in ten and borderline in one. PCR detected the F. tularensis ISFtu2 elements and fopA gene in one rodent and a spring water sample from the same geographic area.

    Conclusions: Based on the clinical manifestations of the disease suggesting an oropharyngeal form of tularemia, serology results in case patients, and F. tularensis detection in the local fauna and aquatic environment, the water supply of the village was the likely source of the tularemia outbreak. Intervention such as dredging and chlorination of the main water storage tank of the village and training of villagers and health care workers in preventive measures and treatment of the illness helped control the infection.

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  • 27.
    Forsell, Joakim
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Bengtsson-Palme, Johan
    Department of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy, and Centre for Antibiotic Resistance Research (CARe), University of Gothenburg, Gothenburg, Sweden.
    Angelin, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Evengård, Birgitta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Granlund, Margareta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    The relation between Blastocystis and the intestinal microbiota in Swedish travellers2017In: BMC Microbiology, E-ISSN 1471-2180, Vol. 17, article id 231Article in journal (Refereed)
    Abstract [en]

    Background: Blastocystis sp. is a unicellular eukaryote that is commonly found in the human intestine. Its ability to cause disease is debated and a subject for ongoing research. In this study, faecal samples from 35 Swedish university students were examined through shotgun metagenomics before and after travel to the Indian peninsula or Central Africa. We aimed at assessing the impact of travel on Blastocystis carriage and seek associations between Blastocystis and the bacterial microbiota.

    Results: We found a prevalence of Blastocystis of 16/35 (46%) before travel and 15/35 (43%) after travel. The two most commonly Blastocystis subtypes (STs) found were ST3 and ST4, accounting for 20 of the 31 samples positive for Blastocystis. No mixed subtype carriage was detected. All ten individuals with a typable ST before and after travel maintained their initial ST. The composition of the gut bacterial community was not significantly different between Blastocystis-carriers and non-carriers. Interestingly, the presence of Blastocystis was accompanied with higher abundances of the bacterial genera Sporolactobacillus and Candidatus Carsonella. Blastocystis carriage was positively associated with high bacterial genus richness, and negatively correlated to the Bacteroides-driven enterotype. These associations were both largely dependent on ST4 – a subtype commonly described from Europe – while the globally prevalent ST3 did not show such significant relationships.

    Conclusions: The high rate of Blastocystis subtype persistence found during travel indicates that long-term carriage of Blastocystis is common. The associations between Blastocystis and the bacterial microbiota found in this study could imply a link between Blastocystis and a healthy microbiota as well as with diets high in vegetables. Whether the associations between Blastocystis and the microbiota are resulting from the presence of Blastocystis, or are a prerequisite for colonization with Blastocystis, are interesting questions for further studies.

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  • 28. Forsman, Mats
    et al.
    Johansson, Anders
    Tularemia (Francisella Tularensis)2005In: Encyclopedia of bioterrorism defense / [ed] Katz, Rebecca;Zilinskas, Raymond A., John Wiley & Sons, 2005, 1, , p. 688Chapter in book (Other academic)
    Abstract [en]

    Tularemia is a zoonosis, a disease of animals transmissible to humans, and is caused by the facultative intracellular bacterium Francisella tularensis. F. tularensis is considered a potential agent of biological warfare and bioterrorism and as such has been rated among the top 6 category A agents. Formerly, F. tularensis was included among agents developed and used by state‐sponsored bioweapons programs. In fact, F. tularensis is one of the most infectious pathogenic bacteria known, requiring inoculation or inhalation of as few as 10 organisms to cause human infection. At present there are four recognized subspecies of F. tularensis: tularensis, holarctica, mediasiatica, and novicida. The natural reservoirs of F. tularensis still await complete delineation. Little is known about the virulence mechanisms of F. tularensis. In a bioterrorism scenario, respiratory tularemia (acquired through inhalation) is judged to be the greatest threat. Natural outbreaks of human respiratory type A or type B tularemia have repeatedly been recorded in farmers and landscape workers illustrating the potential of effective F. tularensis transmission by dry aerosols. The clinical expression of tularemia largely depends on the route of entrance of the infectious agent and the prognosis in tularemia is highly dependent on the causative subspecies of F. tularensis. There is currently no licensed and widely available tularemia vaccine. Tularemia warrants antibiotic treatment and is not transmitted from person to person. Currently, there is a reawakened interest in tularemia and a rapid development of new diagnostics, prophylactics and therapies.

  • 29.
    Furberg, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Tularemia mapping in northernmost Sweden: seroprevalence and a case-control study of risk factors2016In: International Journal of Circumpolar Health, ISSN 1239-9736, E-ISSN 2242-3982, Vol. 75, article id 33200Article in journal (Refereed)
  • 30.
    Furberg, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Xijia, Liu
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Nystedt, Anders
    Stenmark, Stephan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Elisasson, Mats
    Sellin, Mats
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Tularemia in northern Sweden: sero-prevalence and a case-control study of risk factorsManuscript (preprint) (Other academic)
  • 31. Gyuranecz, Miklos
    et al.
    Birdsell, Dawn N.
    Splettstoesser, Wolf
    Seibold, Erik
    Beckstrom-Sternberg, Stephen M.
    Makrai, Laszlo
    Fodor, Laszlo
    Fabbi, Massimo
    Vicari, Nadia
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Busch, Joseph D.
    Vogler, Amy J.
    Keim, Paul
    Wagner, David M.
    Phylogeography of Francisella tularensis subsp holarctica, Europe2012In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 18, no 2, p. 290-293Article in journal (Refereed)
    Abstract [en]

    Francisella tularensis subsp. holarctica isolates from Austria, Germany, Hungary, Italy, and Romania were placed into an existing phylogeographic framework. Isolates from Italy were assigned to phylogenetic group B.FTNF002-00; the other isolates, to group B.13. Most F tularensis subsp. holarctica isolates from Europe belong to these 2 geographically segregated groups.

  • 32. Hernandez, Jorge
    et al.
    Bonnedahl, Jonas
    Eliasson, Ingvar
    Wallensten, Anders
    Comstedt, Pär
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Granholm, Susanne
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Melhus, Asa
    Olsen, Björn
    Drobni, Mirva
    Globally disseminated human pathogenic Escherichia coli of O25b-ST131 clone, harbouring bla(CTX-M-15), found in Glaucous-winged gull at remote Commander Islands, Russia2010In: Environmental Microbiology Reports, ISSN 1758-2229, E-ISSN 1758-2229, Vol. 2, no 2, p. 329-332Article in journal (Refereed)
    Abstract [en]

    With focus on environmental dissemination of antibiotic resistance among clinically relevant bacteria, such as the rising ESBL type of resistance among Escherichia coli, we investigated antibiotic resistance levels in wild birds in the Commander Islands and Kamchatka, Russia. Despite overall low resistance levels in randomly selected E. coli (one from each sample), we found multi-resistant ESBL-producing E. coli harbouring bla(CTX-M-14) and bla(CTX-M-15) using selective screening. Among these multi-resistant ESBL-producing E. coli we found one bla(CTX-M-15) harbouring strain belonging to the O25b-ST131 clone, recognized for its clonal disseminated worldwide as a human pathogen. The potential in acquiring resistant bacteria of human origin, especially highly pathogenic clones, as well as downstream consequences of that, should not be underestimated but further investigated.

  • 33. Hernandez, Jorge
    et al.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Stedt, Johan
    Bengtsson, Stina
    Porczak, Aleksandra
    Granholm, Susanne
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Gonzalez-Acuna, Daniel
    Olsen, Björn
    Bonnedahl, Jonas
    Drobni, Mirva
    Characterization and Comparison of Extended-Spectrum beta-Lactamase (ESBL) Resistance Genotypes and Population Structure of Escherichia coli Isolated from Franklin's Gulls (Leucophaeus pipixcan) and Humans in Chile2013In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 9, p. e76150-Article in journal (Refereed)
    Abstract [en]

    We investigated the general level of antibiotic resistance with further analysis of extended-spectrum beta-lactamase (ESBL) prevalence, as well as the population structure of E. coli in fecal flora of humans and Franklin's gulls (Leucophaeus pipixcan) in central parts of Chile. We found a surprisingly high carriage rate of ESBL-producing E. coli among the gulls 112/372 (30.1%) as compared to the human population 6/49 (12.2%.) Several of the E. coli sequence types (STs) identified in birds have previously been reported as Multi Drug Resistant (MDR) human pathogens including the ability to produce ESBLs. This means that not only commensal flora is shared between birds and humans but also STs with pathogenic potential. Given the migratory behavior of Franklin's gulls, they and other migratory species, may be a part of ESBL dissemination in the environment and over great geographic distances. Apart from keeping the antibiotic use low, breaking the transmission chains between the environment and humans must be a priority to hinder the dissemination of resistance.

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  • 34.
    Hosseinzadeh, Ava
    et al.
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Stylianou, Marios
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Lopes, Jose Pedro
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Müller, Daniel C.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Häggman, André
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Holmberg, Sandra
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Grumaz, Christian
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Sohn, Kai
    Dieterich, Christoph
    Urban, Constantin F.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Stable Redox-Cycling Nitroxide Tempol has Antifungal and Immune-modulatory Properties2019In: Frontiers in Microbiology, E-ISSN 1664-302X, Vol. 10, article id 1843Article in journal (Refereed)
    Abstract [en]

    Invasive mycoses remain underdiagnosed and difficult to treat. Hospitalized individuals with compromised immunity increase in number and constitute the main risk group for severe fungal infections. Current antifungal therapy is hampered by slow and insensitive diagnostics and frequent toxic side effects of standard antifungal drugs. Identification of new antifungal compounds with high efficacy and low toxicity is therefore urgently required. We investigated the antifungal activity of tempol, a cell-permeable nitroxide. To narrow down possible mode of action we used RNA-seq technology and metabolomics to probe for pathways specifically disrupted in the human fungal pathogen Candida albicans due to tempol administration. We found genes upregulated which are involved in iron homeostasis, mitochondrial stress, steroid synthesis, and amino acid metabolism. In an ex vivo whole blood infection, tempol treatment reduced C. albicans colony forming units and at the same time increased the release of pro-inflammatory cytokines, such as interleukin 8 (IL-8, monocyte chemoattractant protein-1, and macrophage migration inhibitory factor). In a systemic mouse model, tempol was partially protective with a significant reduction of fungal burden in the kidneys of infected animals during infection onset. The results obtained propose tempol as a promising new antifungal compound and open new opportunities for the future development of novel therapies.

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  • 35.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Clinical Microbiology. Umeå University, Faculty of Medicine, Clinical Microbiology, Infectious Diseases.
    A genome-wide DNA microarray analysis of Francisella tularensis strains demonstrates extensive genetic conservation within the species but identifies regions that are unique to the highly virulent F. tularensis subspecies tularensis.2002Manuscript (Other academic)
    Abstract [en]

    Francisella tularensis is a potent pathogen and a possible bioterrorism agent. Little is known, however, to explain the molecular basis for its virulence and the distinct differences in virulence found between the four recognized subspecies tularensis, mediaasiatica, holarctica, and novicida. We developed a DNA microarray based on 1,832 clones from a shotgun library used for sequencing of the highly virulent F. tularensis subspecies tularensis, strain Schu S4. This allowed a genome-wide analysis of 27 strains representing all four subspecies. Overall, the microarray analysis confirmed a limited genetic variation within the species F. tularensis, and when strains were compared, at most 3.7 % of the probes showed differential hybridization. Despite marked differences in their virulence and geographical origin, a high genomic similarity between strains of the subspecies tularensis and mediaasiatica was apparent. Within the subspecies holarctica, strains from Japan showed unique hybridization patterns. Eight Regions of Difference (RD), 0.6 - 11.5 kb in size altogether comprising 21 open reading frames, were identified that distinguished strains of the moderately virulent subspecies holarctica and the highly virulent subspecies tularensis, respectively. One of these regions, RD1, allowed for the first time the development of a F. tularensis specific PCR assay discriminating each of the four subspecies.

  • 36.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Clinical Microbiology. Umeå University, Faculty of Medicine, Clinical Microbiology, Infectious Diseases.
    Comparative analysis of PCR versus culture for diagnosis of ulceroglandular tularemia2000In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 38, no 1, p. 22-26Article in journal (Refereed)
    Abstract [en]

    PCR and culture were comparatively evaluated for their abilities to demonstrate Francisella tularensis in wound specimens from tularemia patients during an outbreak in Sweden in 1998. For transport of the specimens used for PCR, a buffer solution containing a nuclease inhibitor was used, and for transport of the specimens used for culture, a commercial transport system was selected after experimental comparison of various systems. Of 40 patients with culture- and/or serology-verified ulceroglandular tularemia, PCR detected F. tularensis DNA in 30 (75%) patients, whereas culture detected bacterial growth in 25 (62%) patients. Compared to data from a previous study, the present inclusion of a nuclease inhibitor in the transport medium did not improve the sensitivity of the PCR, whereas the sensitivity of the culture procedure was significantly increased by selection of the system used for transport. Among eight patients with clinically suspected tularemia but with negative serology and culture, specimens from four patients showed detectable DNA. In three of these patients the diagnosis was verified by the demonstration of an F. tularensis-specific T-cell response in vitro. In conclusion, PCR was more sensitive than culture for demonstration of F. tularensis in wound specimens. Besides, we showed that tularemia may proceed without development of serum antibodies, and in these patients, PCR may be of special importance for verification of the diagnosis.

  • 37.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Clinical Microbiology. Umeå University, Faculty of Medicine, Clinical Microbiology, Infectious Diseases.
    Evaluation of PCR-based methods for discrimination of Francisella species and subspecies and development of a specific PCR that distinguishes the two major subspecies of Francisella tularensis.2000In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 38, no 11, p. 4180-4185Article in journal (Refereed)
    Abstract [en]

    Previous studies have demonstrated that the four subspecies of the human pathogen Francisella tularensis, despite showing marked variations in their virulence for mammals and originating from different regions in the Northern Hemisphere, display a very close phylogenetic relationship. This property has hampered the development of generally applicable typing methods. To overcome this problem, we evaluated the use of PCR for discrimination of the subspecies using various forms of long arbitrary primers or primers specific for repetitive extragenic palindromic sequences (REP) or enterobacterial repetitive intragenic consensus (ERIC) sequences. Patterns generated by use of REP, ERIC, or long arbitrary primers allowed differentiation at the species level and of the four subspecies of F. tularensis. With each of these three methods, similar or identical clustering of strains was found, and groups of strains of different geographical origins or differing in virulence showed distinct patterns. The discriminatory indices of the methods varied from 0.57 to 0.65; thus, the patterns were not sufficiently discriminatory to distinguish individual strains. The sequence of a fragment generated by amplification with an arbitrary primer was determined, and a region showing interstrain heterogeneity was identified. Specific primers were designed, and a PCR was developed that distinguished strains of F. tularensis subsp. holarctica from strains of other F. tularensis subspecies, including strains of the highly virulent F. tularensis subsp. tularensis. Notably, one European isolate showed the genetic pattern typical of the highly virulent F. tularensis subsp. tularensis, generally believed to exist only in North America. It is proposed that a combination of the specific PCR together with one method generating subspecies-specific patterns is suitable as a rapid and relatively simple strategy for discrimination of Francisella species and subspecies.

  • 38.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Clinical Microbiology. Umeå University, Faculty of Medicine, Clinical Microbiology, Infectious Diseases.
    Extensive allelic variation among Francisella tularensis strains in a short-sequence tandem repeat region2001In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 39, no 9, p. 3140-3146Article in journal (Refereed)
    Abstract [en]

    Members of the genus Francisella and the species F. tularensis appear to be genetically very similar despite pronounced differences in virulence and geographic localization, and currently used typing methods do not allow discrimination of individual strains. Here we show that a number of short-sequence tandem repeat (SSTR) loci are present in F. tularensis genomes and that two of these loci, SSTR9 and SSTR16, are together highly discriminatory. Labeled PCR amplification products from the loci were identified by an automated DNA sequencer for size determination, and each allelic variant was sequenced. Simpson's index of diversity was 0.97 based on an analysis of 39 nonrelated F. tularensis isolates. The locus showing the highest discrimination, SSTR9, gave an index of diversity of 0.95. Thirty-two strains isolated from humans during five outbreaks of tularemia showed much less variation. For example, 11 of 12 strains isolated in the Ljusdal area, Sweden in 1995 and 1998 had identical allelic variants. Phenotypic variants of strains and extensively cultured replicates within strains did not differ, and, for example, the same allelic combination was present in 55 isolates of the live-vaccine strain of F. tularensis and another one was present in all 13 isolates of a strain passaged in animals. The analysis of short-sequence repeats of F. tularensis strains appears to be a powerful tool for discrimination of individual strains and may be useful for a detailed analysis of the epidemiology of this potent pathogen.

  • 39.
    Johansson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Celli, Jean
    Conlan, Wayne
    NRC, Canada.
    Elkins, Karen L
    Forsman, Mats
    Swedish Defense Research Agency, Umea, Sweden.
    Keim, Paul S
    Larsson, Pär
    Swedish Defense Research Agency, Umea, Sweden.
    Manoil, Colin
    Nano, Francis E
    Petersen, Jeannine M
    Sjöstedt, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Objections to the transfer of Francisella novicida to the subspecies rank of Francisella tularensis2010In: International Journal of Systematic and Evolutionary Microbiology, ISSN 1466-5026, E-ISSN 1466-5034, Vol. 60, no 8, p. 1717-1718Article in journal (Refereed)
  • 40.
    Johansson, Anders
    et al.
    Umeå University, Faculty of Medicine, Clinical Microbiology, Infectious Diseases.
    Farlow, Jason
    Larsson, Pär
    Umeå University, Faculty of Medicine, Clinical Microbiology, Clinical Bacteriology.
    Dukerich, Meghan
    Chambers, Elias
    Byström, Mona
    Fox, James
    Chu, May
    Forsman, Mats
    FOI, Umeå.
    Sjöstedt, Anders
    Umeå University, Faculty of Medicine, Clinical Microbiology, Clinical Bacteriology.
    Keim, Paul
    Worldwide genetic relationships among Francisella tularensis isolates determined by multiple-locus variable-number tandem repeat analysis.2004In: Journal of Bacteriology, ISSN 0021-9193, E-ISSN 1098-5530, Vol. 186, no 17, p. 5808-5818Article in journal (Refereed)
  • 41.
    Johansson, Anders
    et al.
    Umeå University, Faculty of Medicine, Clinical Microbiology. Umeå University, Faculty of Medicine, Clinical Microbiology, Infectious Diseases.
    Forsman, Mats
    FOI, Umeå.
    Sjöstedt, Anders
    Umeå University, Faculty of Medicine, Clinical Microbiology. Umeå University, Faculty of Medicine, Clinical Microbiology, Clinical Bacteriology.
    The development of tools for diagnosis of tularemia and typing of Francisella tularensis.2004In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 112, no 11-12, p. 898-907Article in journal (Refereed)
  • 42.
    Johansson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Koskiniemi, Satu
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Gottfridsson, Per
    Wiström, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Monsen, Tor
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Multiple-locus variable-number tandem repeat analysis for typing of Staphylococcus epidermidis.2006In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 44, no 1, p. 260-5Article in journal (Refereed)
    Abstract [en]

    We applied a high-resolution PCR-based typing method, multiple-locus variable-number tandem repeat analysis (MLVA), for discrimination of 30 multidrug-resistant clinical isolates of Staphylococcus epidermidis. The results of MLVA were congruent with results obtained by pulsed-field gel electrophoresis (PFGE). MLVA generated discrete character data, and its discriminatory capacity was comparable to that of PFGE.

  • 43.
    Johansson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Lärkeryd, Adrian
    Widerström, Micael
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Mörtberg, Sara
    Myrtännäs, Kerstin
    Ohrman, Caroline
    Birdsell, Dawn
    Keim, Paul
    Wagner, David M
    Forsman, Mats
    Larsson, Pär
    An outbreak of respiratory tularemia caused by diverse clones of Francisella tularensis2014In: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 59, no 11, p. 1546-53Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The bacterium Francisella tularensis is recognized for its virulence, infectivity, genetic homogeneity, and potential as a bioterrorism agent. Outbreaks of respiratory tularemia, caused by inhalation of this bacterium, are poorly understood. Such outbreaks are exceedingly rare, and F. tularensis is seldom recovered from clinical specimens.

    METHODS: A localized outbreak of tularemia in Sweden was investigated. Sixty-seven humans contracted laboratory-verified respiratory tularemia. F. tularensis subspecies holarctica was isolated from the blood or pleural fluid of 10 individuals from July to September 2010. Using whole-genome sequencing and analysis of single-nucleotide polymorphisms (SNPs), outbreak isolates were compared with 110 archived global isolates.

    RESULTS: There were 757 SNPs among the genomes of the 10 outbreak isolates and the 25 most closely related archival isolates (all from Sweden/Finland). Whole genomes of outbreak isolates were >99.9% similar at the nucleotide level and clustered into 3 distinct genetic clades. Unexpectedly, high-sequence similarity grouped some outbreak and archival isolates that originated from patients from different geographic regions and up to 10 years apart. Outbreak and archival genomes frequently differed by only 1-3 of 1 585 229 examined nucleotides.

    CONCLUSIONS: The outbreak was caused by diverse clones of F. tularensis that occurred concomitantly, were widespread, and apparently persisted in the environment. Multiple independent acquisitions of F. tularensis from the environment over a short time period suggest that natural outbreaks of respiratory tularemia are triggered by environmental cues. The findings additionally caution against interpreting genome sequence identity for this pathogen as proof of a direct epidemiological link.

  • 44.
    Johansson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Petersen, Jeannine M
    Genotyping of Francisella tularensis, the causative agent of tularemia2010In: Journal of AOAC International, ISSN 1060-3271, E-ISSN 1944-7922, Vol. 93, no 6, p. 1930-1943Article in journal (Refereed)
    Abstract [en]

    Francisella tularensis is a facultative, intracellular, zoonotic pathogen and the causative agent of tularemia. Historically, F. tularensis has been subdivided into subspecies on the basis of phenotypic traits, including biochemical reactivity and virulence. More recently, a number of genotypic methods, ranging from relatively insensitive methods to full genome sequencing, have been used to investigate genetic diversity within F. tularensis. These analyses indicate that F. tularensis is a pathogen of low sequence diversity with pair-wise average nucleotide identities > 99.2% across subspecies. Nonetheless, genomic rearrangements and sequence deletions exist between and within F. tularensis subspecies, creating polymorphisms detectable by genotyping methods. Genetic subpopulations intermediate to the subspecies and strain level have been identified within F. tularensis subsp. tularensis and F. tularensis subsp. holarctica by several different typing methods. These genetic subpopulations have been associated with differences in disease severity, geographic distribution, and transmission patterns. For example, one F. tularensis subsp. tularensis subpopulation has been found to be significantly associated with mortality in humans. Additionally, genotypic analyses of Francisella spp. have provided information for use in the rational design of strain panels for validation of F. tularensis diagnostic tests. This review provides a guide to the various F. tularensis genotyping methods.

  • 45.
    Johansson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Tomaso, Herbert
    Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Bacterial Infections and Zoonoses, Naumburger Strasse 96a, Jena 07743, United Kingdom.
    Padeshki, Plamen
    National Center of Infectious and Parasitic Diseases, Department of Microbiology, 26 Yanko Sakazov Blvd, 1504 Sofia, Bulgaria.
    Sjöstedt, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Silman, Nigel
    Health Protection Agency, Microbiology Services, Porton Down, Salisbury SP4 0JG, United Kingdom.
    Pilo, Paola
    University of Bern, Institute for Veterinary Bacteriology, Department of Infections Diseases and Pathobiology, Länggasstrasse 122, Bern 3012, Switzerland.
    Francisella tularensis: Tularemia2012In: BSL3 and BSL4 agents: epidemiology, microbiology, and practical guidelines / [ed] Mandy C. Elschner; Sally J. Cutler; Manfred Weidmann; Patrick Butaye, Wiley-VCH Verlagsgesellschaft, 2012, p. 71-84Chapter in book (Refereed)
    Abstract [en]

    Francisella tularensis is the causative agent of tularemia. This emerging zoonosis shows several clinical manifestations complicating its diagnosis. The chapter focus on the characteristics of this bacterium, the several forms of the disease, its diagnosis and molecular epidemiology.

  • 46.
    Johansson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Tomaso, Herbert
    Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Bacterial Infections and Zoonoses, Naumburger Strasse 96a, Jena 07743, United Kingdom.
    Padeshki, Plamen
    National Center of Infectious and Parasitic Diseases, Department of Microbiology, 26 Yanko Sakazov Blvd., 1504 Sofia, Bulgaria.
    Sjöstedt, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Silman, Nigel
    Health Protection Agency, Microbiology Services, Porton Down, Salisbury SP4 0JG, United Kingdom.
    Pilo, Paola
    University of Bern, Institute for Veterinary Bacteriology, Department of Infections Diseases and Pathobiology, Länggasstrasse 122, Bern 3012, Switzerland.
    Francisella tularensis: Tularemia2012In: BSL3 and BSL4 agents: epidemiology, microbiology, and practical guidelines / [ed] Mandy C. Elschner; Sally J. Cutler; Manfred Weidmann; Patrick Butaye, Wiley-VCH Verlagsgesellschaft, 2012, p. 309-311Chapter in book (Refereed)
    Abstract [en]

    This practical guide gives some starting points to manage biological safety issues with Francisella tularensis.

  • 47.
    Johnning, Anna
    et al.
    Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden; Department of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden.
    Kristiansson, Erik
    Department of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden .
    Angelin, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Marathe, Nachiket
    Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden; Microbial Culture Collection, National Centre for Cell Science, Pune, India .
    Shouche, Yogesh S.
    Microbial Culture Collection, National Centre for Cell Science, Pune, India .
    Johansson, Anders
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Larsson, D. G. Joakim
    Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden .
    Quinolone resistance mutations in the faecal microbiota of Swedish travellers to India2015In: BMC Microbiology, E-ISSN 1471-2180, Vol. 15, article id 235Article in journal (Refereed)
    Abstract [en]

    Background: International travel contributes to the spread of antibiotic resistant bacteria over the world. Most studies addressing travel-related changes in the faecal flora have focused on specific mobile resistance genes, or depended on culturing of individual bacterial isolates. Antibiotic resistance can, however, also spread via travellers colonized by bacteria carrying chromosomal antibiotic resistance mutations, but this has received little attention so far. Here we aimed at exploring the abundance of chromosomal quinolone resistance mutations in Escherichia communities residing in the gut of Swedish travellers, and to determine potential changes after visiting India. Sweden is a country with a comparably low degree of quinolone use and quinolone resistance, whereas the opposite is true for India. Methods: Massively parallel amplicon sequencing targeting the quinolone-resistance determining region of gyrA and parC was applied to total DNA extracted from faecal samples. Paired samples were collected from 12 Swedish medical students before and after a 4-15 week visit to India. Twelve Indian residents were included for additional comparisons. Methods known resistance mutations were common in Swedes before travel as well as in Indians, with a trend for all mutations to be more common in the Indian sub group. There was a significant increase in the abundance of the most common amino acid substitution in GyrA (S83L, from 44 to 72 %, p = 0.036) in the samples collected after return to Sweden. No other substitution, including others commonly associated with quinolone resistance (D87N in GyrA, S80I in ParC) changed significantly. The number of distinct genotypes encoded in each traveller was significantly reduced after their visit to India for both GyrA (p = 0.0020) and ParC (p = 0.0051), indicating a reduced genetic diversity, similar to that found in the Indians. Conclusions: International travel can alter the composition of the Escherichia communities in the faecal flora, favouring bacteria carrying certain resistance mutations, and, thereby, contributes to the global spread of antibiotic resistance. A high abundance of specific mutations in Swedish travellers before visiting India is consistent with the hypothesis that these mutation have no fitness cost even in the absence of an antibiotic selection pressure.

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  • 48. Karadenizli, A.
    et al.
    Forsman, M.
    Simsek, H.
    Taner, M.
    Ohrman, C.
    Myrtennas, K.
    Larkeryd, A.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Ozdemir, L.
    Sjodin, A.
    Genomic analyses of Francisella tularensis strains confirm disease transmission from drinking water sources, Turkey, 2008, 2009 and 20122015In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 20, no 21Article in journal (Refereed)
    Abstract [en]

    Waterborne epidemics of tularaemia caused by Francisella tularensis are increasingly reported in Turkey. We have used whole genome sequencing to investigate if F. tularensis isolated from patients could be traced back to drinking water sources. Tonsil swabs from 33 patients diagnosed with oropharyngeal tularaemia in three outbreaks and 140 water specimens were analysed. F. tularensis subsp. holarctica was confirmed by microagglutination and PCR in 12 patients and five water specimens. Genomic analysis of three pairs of patient and water isolates from outbreaks in Sivas, Corum, and Kocaeli showed the isolates to belong to two new clusters of the F. tularensis B. 12 genetic clade. The clusters were defined by 19 and 15 single nucleotide polymorphisms (SNPs) in a multiple alignment based on 507 F. tularensis genomes. One synonymous SNP was chosen as a new canonical SNP (canSNP) for each cluster for future use in diagnostic assays. No SNP was identified between the genomes from the patient-water pair of isolates from Kocaeli, one SNP between the pair of isolates from Sivas, whereas the pair from Corum differed at seven SNPs. These results illustrate the power of whole genome sequencing for tracing F. tularensis patient isolates back to their environmental source.

  • 49.
    Karah, Nabil
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Dwibedi, Chinmay Kumar
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Sjöström, Karin
    Edquist, Petra
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Wai, Sun Nyunt
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Uhlin, Bernt Eric
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Novel Aminoglycoside Resistance Transposons and Transposon-Derived Circular Forms Detected in Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates2016In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 60, no 3, p. 1801-1818Article in journal (Refereed)
    Abstract [en]

    Acinetobacter baumannii has emerged as an important opportunistic pathogen equipped with a growing number of antibiotic resistance genes. Our study investigated the molecular epidemiology and antibiotic resistance features of 28 consecutive carbapenem-resistant clinical isolates of A. baumannii collected throughout Sweden in 2012 and 2013. The isolates mainly belonged to clonal complexes (CCs) with an extensive international distribution, such as CC2 (n = 16) and CC25 (n = 7). Resistance to carbapenems was related to bla(OXA-23) (20 isolates), bla(OXA-24/40-like) (6 isolates), bla(OXA-467) (1 isolate), and ISAba1-bla(OXA-69) (1 isolate). Ceftazidime resistance was associated with bla(PER-7) in the CC25 isolates. Two classical point mutations were responsible for resistance to quinolones in all the isolates. Isolates with high levels of resistance to aminoglycosides carried the 16S rRNA methylase armA gene. The isolates also carried a variety of genes encoding aminoglycoside-modifying enzymes. Several novel structures involved in aminoglycoside resistance were identified, including Tn6279, Delta Tn6279, Ab-ST3- aadB, and different assemblies of Tn6020 and TnaphA6. Importantly, a number of circular forms related to the IS26 or ISAba125 composite trans-posons were detected. The frequent occurrence of these circular forms in the populations of several isolates indicates a potential role of these circular forms in the dissemination of antibiotic resistance genes.

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  • 50. Karlsson, Edvin
    et al.
    Golovliov, Igor
    Lärkeryd, Adrian
    Granberg, Malin
    Larsson, Eva
    Öhrman, Caroline
    Niemcewicz, Marcin
    Birdsell, Dawn
    Wagner, David M.
    Forsman, Mats
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Clonality of erythromycin resistance in Francisella tularensis2016In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, no 10, p. 2815-2823Article in journal (Refereed)
    Abstract [en]

    Objectives: We analysed diverse strains of Francisella tularensis subsp. holarctica to assess if its division into biovars I and II is associated with specific mutations previously linked to erythromycin resistance and to determine the distribution of this resistance trait across this subspecies. Methods:Three-hundred and fourteen F. tularensis subsp. holarctica strains were tested for erythromycin susceptibility and whole-genome sequences for these strains were examined for SNPs in genes previously associated with erythromycin resistance. Each strain was assigned to a global phylogenetic framework using genome-wide canonical SNPs. The contribution of a specific SNP to erythromycin resistance was examined using allelic exchange. The geographical distribution of erythromycin-resistant F. tularensis strains was further investigated by literature search. Results:There was a perfect correlation between biovar II strains (erythromycin resistance) and the phylogenetic group B.12. Only B.12 strains had an AaEuroS -> aEuroSC SNP at position 2059 in the three copies of the rrl gene. Introducing 2059C into an rrl gene of an erythromycin-susceptible F. tularensis strain resulted in resistance. An additional 1144 erythromycin-resistant strains were identified from the scientific literature, all of them from Eurasia. Conclusions:Erythromycin resistance in F. tularensis is caused by an A2059C rrl gene mutation, which exhibits a strictly clonal inheritance pattern found only in phylogenetic group B.12. This group is an extremely successful clone, representing the most common type of F. tularensis throughout Eurasia.

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