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  • 1. Afset, J. E.
    et al.
    Larssen, K. W.
    Bergh, K.
    Larkeryd, A.
    Sjodin, A.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Forsman, M.
    Phylogeographical pattern of Francisella tularensis in a nationwide outbreak of tularaemia in Norway, 20112015Ingår i: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 20, nr 19, s. 9-14, artikel-id 21125Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Forsman, Mats
    Larsson, Pär
    Sjödin, Andreas
    Increased knowledge of Francisella genus diversity highlights the benefits of optimised DNA-based assays2012Ingår i: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 12, s. 220-Artikel i tidskrift (Refereegranskat)
    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.

  • 3.
    Angelin, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Forsell, Joakim
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Granlund, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Evengård, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Palmgren, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Risk factors for colonization with extended-spectrum beta-lactamase producing Enterobacteriaceae in healthcare students on clinical assignment abroad: A prospective study2015Ingår i: Travel Medicine and Infectious Disease, ISSN 1477-8939, E-ISSN 1873-0442, Vol. 13, nr 3, s. 223-229Artikel i tidskrift (Refereegranskat)
    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 universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Fahlgren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Näsström, Elin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Kouremenos, Konstantinos
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Sundén-Cullberg, Jonas
    Guo, Yongzhi
    Moritz, Thomas
    Wolf-Watz, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Fällman, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Metabolic profiling for detection of staphylococcus aureus infection and antibiotic resistance2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 2, artikel-id e56971Artikel i tidskrift (Refereegranskat)
    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.

  • 5. Ariza-Miguel, Jaime
    et al.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Fernández-Natal, María Isabel
    Martínez-Nistal, Carmen
    Orduña, Antonio
    Rodríguez-Ferri, Elías F
    Hernández, Marta
    Rodríguez-Lázaro, David
    Molecular investigation of tularemia outbreaks, Spain, 1997-20082014Ingår i: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 20, nr 5, s. 754-761Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Huss, Mikael
    Kjellqvist, Sanela
    Kristiansson, Erik
    Palmgren, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Larsson, D. G. Joakim
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    The Human Gut Microbiome as a Transporter of Antibiotic Resistance Genes between Continents2015Ingår i: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 59, nr 10, s. 6551-6560Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (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 patients2018Ingår i: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 18, artikel-id 319Artikel i tidskrift (Refereegranskat)
    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.

  • 8. Birdsell, Dawn N
    et al.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    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 States2014Ingår i: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 20, nr 5, s. 861-865Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Szilagyi, E.
    Lucet, J. -C
    Overcoming the obstacles of implementing infection prevention and control guidelines2015Ingår i: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 21, nr 12, s. 1067-1071Artikel, forskningsöversikt (Refereegranskat)
    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. Bonnedahl, J
    et al.
    Drobni, P
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    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 Sweden2010Ingår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 65, nr 9, s. 1939-1944Artikel i tidskrift (Refereegranskat)
    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.

  • 11. Bonnedahl, Jonas
    et al.
    Drobni, Mirva
    Gauthier-Clerc, Michel
    Hernandez, Jorge
    Granholm, Susanne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Kayser, Yves
    Melhus, Asa
    Kahlmeter, Gunnar
    Waldenström, Jonas
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Olsen, Björn
    Uppsala universitet.
    Dissemination of Escherichia coli with CTX-M type ESBL between humans and yellow-legged gulls in the south of France2009Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 4, nr 6, s. e5958-Artikel i tidskrift (Refereegranskat)
    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.

  • 12. Byström, Mona
    et al.
    Böcher, Sidsel
    Magnusson, Anna
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Infektionssjukdomar.
    Prag, Jørgen
    Johansson, Anders
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Infektionssjukdomar.
    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.2005Ingår i: Journal of Clinical Microbiology, ISSN 0095-1137, Vol. 43, nr 10, s. 5355-8Artikel i tidskrift (Refereegranskat)
    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.

  • 13.
    Desvars, Amélie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Furberg, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Hjertqvist, Marika
    Vidman, Linda
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Sjöstedt, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Rydén, Patrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Epidemiology and Ecology of Tularemia in Sweden2015Ingår i: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 44, s. 58-58Artikel i tidskrift (Övrigt vetenskapligt)
  • 14.
    Desvars, Amélie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Furberg, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Hjertqvist, Marika
    Vidman, Linda
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Sjöstedt, Anders
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Rydén, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Epidemiology and Ecology of Tularemia in Sweden, 1984-20122015Ingår i: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 21, nr 1, s. 32-39Artikel i tidskrift (Refereegranskat)
    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.

  • 15.
    Dwibedi, Chinmay Kumar
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (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 universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Long-range dispersal moved Francisella tularensis into Western Europe from the East2016Ingår i: Microbial Genomics, ISSN 2057-5858, Vol. 2, nr 12Artikel i tidskrift (Refereegranskat)
    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.

  • 16.
    Edin, Alicia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Granholm, Susanne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Koskiniemi, Satu
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Allard, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Sjöstedt, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Development and Laboratory Evaluation of a Real-Time PCR Assay for Detecting Viruses and Bacteria of Relevance for Community-Acquired Pneumonia2015Ingår i: Journal of Molecular Diagnostics, ISSN 1525-1578, E-ISSN 1943-7811, Vol. 17, nr 3, s. 315-324Artikel i tidskrift (Refereegranskat)
    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.

  • 17.
    Forsell, Joakim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    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 universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Evengård, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Granlund, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    The relation between Blastocystis and the intestinal microbiota in Swedish travellers2017Ingår i: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 17, artikel-id 231Artikel i tidskrift (Refereegranskat)
    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.

  • 18. Forsman, Mats
    et al.
    Johansson, Anders
    Tularemia (Francisella Tularensis)2005Ingår i: Encyclopedia of bioterrorism defense / [ed] Katz, Rebecca;Zilinskas, Raymond A., John Wiley & Sons, 2005, 1, , s. 688Kapitel i bok, del av antologi (Övrigt vetenskapligt)
    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.

  • 19.
    Furberg, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Tularemia mapping in northernmost Sweden: seroprevalence and a case-control study of risk factors2016Ingår i: International Journal of Circumpolar Health, ISSN 1239-9736, E-ISSN 2242-3982, Vol. 75, artikel-id 33200Artikel i tidskrift (Refereegranskat)
  • 20.
    Furberg, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Xijia, Liu
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Nystedt, Anders
    Stenmark, Stephan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Elisasson, Mats
    Sellin, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Johansson, Andersson
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Tularemia in northern Sweden - sero-prevalence and a case-control study of risk factorsArtikel i tidskrift (Refereegranskat)
  • 21. 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 universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Busch, Joseph D.
    Vogler, Amy J.
    Keim, Paul
    Wagner, David M.
    Phylogeography of Francisella tularensis subsp holarctica, Europe2012Ingår i: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 18, nr 2, s. 290-293Artikel i tidskrift (Refereegranskat)
    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.

  • 22. Hernandez, Jorge
    et al.
    Bonnedahl, Jonas
    Eliasson, Ingvar
    Wallensten, Anders
    Comstedt, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Granholm, Susanne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    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, Russia2010Ingår i: Environmental Microbiology Reports, ISSN 1758-2229, E-ISSN 1758-2229, Vol. 2, nr 2, s. 329-332Artikel i tidskrift (Refereegranskat)
    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.

  • 23. Hernandez, Jorge
    et al.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Stedt, Johan
    Bengtsson, Stina
    Porczak, Aleksandra
    Granholm, Susanne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    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 Chile2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 9, s. e76150-Artikel i tidskrift (Refereegranskat)
    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.

  • 24.
    Hosseinzadeh, Ava
    et al.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Stylianou, Marios
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Lopes, Jose Pedro
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Müller, Daniel C.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Häggman, André
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Holmberg, Sandra
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Grumaz, Christian
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Sohn, Kai
    Dieterich, Christoph
    Urban, Constantin F.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Stable Redox-Cycling Nitroxide Tempol has Antifungal and Immune-modulatory Properties2019Ingår i: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 10, artikel-id 1843Artikel i tidskrift (Refereegranskat)
    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.

  • 25.
    Johansson, Anders
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi. Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Infektionssjukdomar.
    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.2002Manuskript (Övrigt vetenskapligt)
    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.

  • 26.
    Johansson, Anders
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi. Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Infektionssjukdomar.
    Comparative analysis of PCR versus culture for diagnosis of ulceroglandular tularemia2000Ingår i: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 38, nr 1, s. 22-26Artikel i tidskrift (Refereegranskat)
    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.

  • 27.
    Johansson, Anders
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi. Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Infektionssjukdomar.
    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.2000Ingår i: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 38, nr 11, s. 4180-4185Artikel i tidskrift (Refereegranskat)
    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.

  • 28.
    Johansson, Anders
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi. Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Infektionssjukdomar.
    Extensive allelic variation among Francisella tularensis strains in a short-sequence tandem repeat region2001Ingår i: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 39, nr 9, s. 3140-3146Artikel i tidskrift (Refereegranskat)
    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.

  • 29.
    Johansson, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    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 universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Objections to the transfer of Francisella novicida to the subspecies rank of Francisella tularensis2010Ingår i: International Journal of Systematic and Evolutionary Microbiology, ISSN 1466-5026, E-ISSN 1466-5034, Vol. 60, nr 8, s. 1717-1718Artikel i tidskrift (Refereegranskat)
  • 30.
    Johansson, Anders
    et al.
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Infektionssjukdomar.
    Farlow, Jason
    Larsson, Pär
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Klinisk bakteriologi.
    Dukerich, Meghan
    Chambers, Elias
    Byström, Mona
    Fox, James
    Chu, May
    Forsman, Mats
    FOI, Umeå.
    Sjöstedt, Anders
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Klinisk bakteriologi.
    Keim, Paul
    Worldwide genetic relationships among Francisella tularensis isolates determined by multiple-locus variable-number tandem repeat analysis.2004Ingår i: Journal of Bacteriology, ISSN 0021-9193, E-ISSN 1098-5530, Vol. 186, nr 17, s. 5808-5818Artikel i tidskrift (Refereegranskat)
  • 31.
    Johansson, Anders
    et al.
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi. Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Infektionssjukdomar.
    Forsman, Mats
    FOI, Umeå.
    Sjöstedt, Anders
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi. Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Klinisk bakteriologi.
    The development of tools for diagnosis of tularemia and typing of Francisella tularensis.2004Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 112, nr 11-12, s. 898-907Artikel i tidskrift (Refereegranskat)
  • 32.
    Johansson, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Koskiniemi, Satu
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Gottfridsson, Per
    Wiström, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Monsen, Tor
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Multiple-locus variable-number tandem repeat analysis for typing of Staphylococcus epidermidis.2006Ingår i: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 44, nr 1, s. 260-5Artikel i tidskrift (Refereegranskat)
    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.

  • 33.
    Johansson, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Lärkeryd, Adrian
    Widerström, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    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 tularensis2014Ingår i: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 59, nr 11, s. 1546-53Artikel i tidskrift (Refereegranskat)
    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.

  • 34.
    Johansson, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Petersen, Jeannine M
    Genotyping of Francisella tularensis, the causative agent of tularemia2010Ingår i: Journal of AOAC International, ISSN 1060-3271, E-ISSN 1944-7922, Vol. 93, nr 6, s. 1930-1943Artikel i tidskrift (Refereegranskat)
    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.

  • 35.
    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 universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    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 universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (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 India2015Ingår i: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 15, artikel-id 235Artikel i tidskrift (Refereegranskat)
    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.

  • 36. Karadenizli, A.
    et al.
    Forsman, M.
    Simsek, H.
    Taner, M.
    Ohrman, C.
    Myrtennas, K.
    Larkeryd, A.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Ozdemir, L.
    Sjodin, A.
    Genomic analyses of Francisella tularensis strains confirm disease transmission from drinking water sources, Turkey, 2008, 2009 and 20122015Ingår i: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 20, nr 21Artikel i tidskrift (Refereegranskat)
    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.

  • 37.
    Karah, Nabil
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Dwibedi, Chinmay Kumar
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Sjöström, Karin
    Edquist, Petra
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Wai, Sun Nyunt
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Uhlin, Bernt Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Novel Aminoglycoside Resistance Transposons and Transposon-Derived Circular Forms Detected in Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates2016Ingår i: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 60, nr 3, s. 1801-1818Artikel i tidskrift (Refereegranskat)
    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.

  • 38. 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 universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Clonality of erythromycin resistance in Francisella tularensis2016Ingår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, nr 10, s. 2815-2823Artikel i tidskrift (Refereegranskat)
    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.

  • 39. Karlsson, Edvin
    et al.
    Svensson, Kerstin
    Lindgren, Petter
    Byström, Mona
    Sjödin, Andreas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Forsman, Mats
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    The phylogeographic pattern of Francisella tularensis in Sweden indicates a Scandinavian origin of Eurosiberian tularaemia2013Ingår i: Environmental Microbiology, ISSN 1462-2912, E-ISSN 1462-2920, Vol. 15, nr 2, s. 634-645Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Previous studies of the causative agent of tularaemia, Francisella tularensis have identified phylogeographic patterns suggestive of environmental maintenance reservoirs. To investigate the phylogeography of tularaemia in Sweden, we selected 163 clinical isolates obtained during 1995-2009 in 10 counties and sequenced one isolate's genome to identify new genetic markers. An improved typing scheme based on two indels and nine SNPs was developed using hydrolysis or TaqMan MGB probe assays. The results showed that much of the known global genetic diversity of F. tularensis subsp. holarctica is present in Sweden. Thirteen of the 163 isolates belonged to a new genetic group that is basal to all other known members of the major genetic clade B.I, which is spread across the Eurosiberian region. One hundred and twenty-five of the 163 Swedish isolates belonged to B.I, but individual clades' frequencies differed from county to county (P < 0.001). Subsequent analyses revealed a correlation between genotype variation over time and recurrent outbreaks at specific places, supporting the 'maintenance reservoir' environmental maintenance hypothesis. Most importantly, the findings reveal the presence of diverse source populations of F. tularensis subsp. holarctica in Sweden and suggest a historical spread of the disease from Scandinavia to other parts of Eurosiberia.

  • 40.
    Kroca, Michal
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Sjöstedt, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Tärnvik, Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Vγ9Vδ2 T cells from individuals undergoing Pontiac fever or tularemia respond at a similar extent to phosphoantigen from Francisella tularensis or Legionella micdadei.Manuskript (Övrig (populärvetenskap, debatt, mm))
  • 41.
    Larsson, Pär
    et al.
    Swedish Defense Research Agency, Umeå, Sweden.
    Elfsmark, Daniel
    Swedish Defense Research Agency, Umeå, Sweden.
    Svensson, Kerstin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Wikström, Per
    Swedish Defense Research Agency, Umeå, Sweden.
    Forsman, Mats
    Swedish Defense Research Agency, Umeå, Sweden.
    Brettin, Thomas
    Keim, Paul
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Molecular evolutionary consequences of niche restriction in Francisella tularensis, a facultative intracellular pathogen2009Ingår i: PLoS pathogens, ISSN 1553-7374, Vol. 5, nr 6, s. e1000472-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Francisella tularensis is a potent mammalian pathogen well adapted to intracellular habitats, whereas F. novicida and F. philomiragia are less virulent in mammals and appear to have less specialized lifecycles. We explored adaptations within the genus that may be linked to increased host association, as follows. First, we determined the genome sequence of F. tularensis subsp. mediasiatica, the only subspecies that had not been previously sequenced. This genome, and those of 12 other F. tularensis isolates, were then compared to the genomes of F. novicida (three isolates) and F. philomiragia (one isolate). Signs of homologous recombination were found in approximately 19.2% of F. novicida and F. philomiragia genes, but none among F. tularensis genomes. In addition, random insertions of insertion sequence elements appear to have provided raw materials for secondary adaptive mutations in F. tularensis, e.g. for duplication of the Francisella Pathogenicity Island and multiplication of a putative glycosyl transferase gene. Further, the five major genetic branches of F. tularensis seem to have converged along independent routes towards a common gene set via independent losses of gene functions. Our observations suggest that despite an average nucleotide identity of >97%, F. tularensis and F. novicida have evolved as two distinct population lineages, the former characterized by clonal structure with weak purifying selection, the latter by more frequent recombination and strong purifying selection. F. tularensis and F. novicida could be considered the same bacterial species, given their high similarity, but based on the evolutionary analyses described in this work we propose retaining separate species names.

  • 42. Lindgren, Petter
    et al.
    Myrtennäs, Kerstin
    Forsman, Mats
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Stenberg, Per
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap. Department of Biological Agents, Division of CBRN Defence and Security, Swedish Defence Research Agency (FOI), SE-901 82 Umeå, Sweden.
    Nordgaard, Anders
    Ahlinder, Jon
    A likelihood ratio-based approach for improved source attribution in microbiological forensic investigations2019Ingår i: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 302, artikel-id 109869Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A common objective in microbial forensic investigations is to identify the origin of a recovered pathogenic bacterium by DNA sequencing. However, there is currently no consensus about how degrees of belief in such origin hypotheses should be quantified, interpreted, and communicated to wider audiences. To fill this gap, we have developed a concept based on calculating probabilistic evidential values for microbial forensic hypotheses. The likelihood-ratio method underpinning this concept is widely used in other forensic fields, such as human DNA matching, where results are readily interpretable and have been successfully communicated in juridical hearings. The concept was applied to two case scenarios of interest in microbial forensics: (1) identifying source cultures among series of very similar cultures generated by parallel serial passage of the Tier 1 pathogen Francisella tularensis, and (2) finding the production facilities of strains isolated in a real disease outbreak caused by the human pathogen Listeria monocytogenes. Evidence values for the studied hypotheses were computed based on signatures derived from whole genome sequencing data, including deep-sequenced low-frequency variants and structural variants such as duplications and deletions acquired during serial passages. In the F. tularensis case study, we were able to correctly assign fictive evidence samples to the correct culture batches of origin on the basis of structural variant data. By setting up relevant hypotheses and using data on cultivated batch sources to define the reference populations under each hypothesis, evidential values could be calculated. The results show that extremely similar strains can be separated on the basis of amplified mutational patterns identified by high-throughput sequencing. In the L. monocytogenes scenario, analyses of whole genome sequence data conclusively assigned the clinical samples to specific sources of origin, and conclusions were formulated to facilitate communication of the findings. Taken together, these findings demonstrate the potential of using bacterial whole genome sequencing data, including data on both low frequency SNP signatures and structural variants, to calculate evidence values that facilitate interpretation and communication of the results. The concept could be applied in diverse scenarios, including both epidemiological and forensic source tracking of bacterial infectious disease outbreaks. 

  • 43.
    Lärkeryd, Adrian
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Myrtennäs, Kerstin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Division of CBRN Security and Defence, FOI, Swedish Defence Research Agency.
    Karlsson, Edvin
    Division of CBRN Security and Defence, FOI, Swedish Defence Research Agency.
    Dwibedi, Chinmay Kumar
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Division of CBRN Security and Defence, FOI, Swedish Defence Research Agency.
    Forsman, Mats
    Division of CBRN Security and Defence, FOI, Swedish Defence Research Agency.
    Larsson, Pär
    Division of CBRN Security and Defence, FOI, Swedish Defence Research Agency.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Sjödin, Andreas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    CanSNPer: a hierarchical genotype classifier of clonal pathogens2014Ingår i: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 30, nr 12, s. 1762-1764Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Advances in typing methodologies have recently reformed the field of molecular epidemiology of pathogens. The falling cost of sequencing technologies is creating a deluge of whole genome sequencing data that burdens bioinformatics resources and tool development. In particular, single nucleotide polymorphisms in core genomes of pathogens are recognized as the most important markers for inferring genetic relationships because they are evolutionarily stable and amenable to high-throughput detection methods. Sequence data will provide an excellent opportunity to extend our understanding of infectious disease when the challenge of extracting knowledge from available sequence resources is met. Here, we present an efficient and user-friendly genotype classification pipeline, CanSNPer, based on an easily expandable database of predefined canonical single nucleotide polymorphisms.

  • 44. Mostafavi, Ehsan
    et al.
    Ghasemi, Ahmad
    Rohani, Mahdi
    Molaeipoor, Leila
    Esmaeili, Saber
    Mohammadi, Zeinolabedin
    Mahmoudi, Ahmad
    Aliabadian, Mansour
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Molecular Survey of Tularemia and Plague in Small Mammals From Iran2018Ingår i: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 8, artikel-id 215Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Plague and tularemia are zoonoses and their causative bacteria are circulating in certain regions of Iran. This study was conducted to investigate potential disease reservoirs amongst small wildlife species in different regions of Iran.

    Methods: Rodents, insectivores and hares from 17 different provinces of the country were collected in 2014 and 2015. Samples were taken from the spleens of the animals and Real-time PCR was applied to detect nucleic acid sequences that are specific to Francisella tularensis and Yersinia pestis, respectively.

    Results: Among 140 collected rodents, 25 distinct species were identified out of which five were the most common: Microtus paradoxus (21% out of 140 rodents), Apodemus witherbyi (12%), Microtus irani (11%), Mus musculus (11%) and Microtus socialis (10%). Seventeen insectivores were collected and identified as Crocidura suaveolens (82%) and C. leucodon (18%). Fifty-one hares were collected and identified as Lepus europaeus (57%), Lepus tolai (14%) and Lepus sp. (29%). Three out of 140 explored rodents (1.91%) were positive for F. tularensis, an A. witherbyi, a Mus musculus domesticus, and a Chionomys nivalis collected from Golestan, Khuzestan and Razavi Khorasan provinces, respectively. Two hares (3.92%) were F. tularensis-positive, a L. europaeus from Khuzestan and a Lepus sp. from the Sistan and Baluchistan province. None of the tested animals were positive for Y. pestis.

    Conclusion: This is the first report of direct detection of F. tularensis in mammals of Iran and the first-time observation of the agent in a snow vole, C. nivalis worldwide. The results indicate that tularemia is more widespread in Iran than previously reported including the Northeast and Southwestern parts of the country. Future studies should address genetic characterization of F. tularensis positive DNA samples from Iran to achieve molecular subtyping and rule out assay cross-reactivity with near neighbor Francisella species.

  • 45.
    Myrtennäs, Kerstin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar. FOI.
    Sjödin, Andreas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Byström, Mona
    Granberg, Malin
    Brittnacher, Mitchell J.
    Rohmer, Laurence
    Jacobs, Michael A.
    Sims-Day, Elizabeth H.
    Levy, Ruth
    Zhou, Yang
    Hayden, Hillary S.
    Lim, Regina
    Chang, Jean
    Guenthener, Donald
    Kang, Allison
    Haugen, Eric
    Gillett, Will
    Kaul, Rajinder
    Forsman, Mats
    Larsson, Par
    FOI.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Genome sequence of Francisella Tularensis subspecies holarctica Strain FSC200, isolated from a child with Tularemia2012Ingår i: Journal of Bacteriology, ISSN 0021-9193, E-ISSN 1098-5530, Vol. 194, nr 24, s. 6965-6966Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Here we report the complete, accurate 1.89-Mb genome sequence of Francisella tularensis subsp. holarctica strain FSC200, isolated in 1998 in the Swedish municipality Ljusdal, which is in an area where tularemia is highly endemic. This genome is important because strain FSC200 has been extensively used for functional and genetic studies of Francisella and is well-characterized.

  • 46.
    Müller, Daniel C.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Kauppi, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Edin, Alicia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Gylfe, Åsa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Sjöstedt, Anders B.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Phospholipid Levels in Blood during Community-Acquired Pneumonia2019Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, nr 5, artikel-id e0216379Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Phospholipids, major constituents of bilayer cell membranes, are present in large amounts in pulmonary surfactant and play key roles in cell signaling. Here, we aim at finding clinically useful disease markers in community-acquired pneumonia (CAP) using comprehensive phospholipid profiling in blood and modeling of changes between sampling time points. Serum samples from 33 patients hospitalized with CAP were collected at admission, three hours after the start of intravenous antibiotics, Day 1 (at 12–24 h), Day 2 (at 36–48 h), and several weeks after recovery. A profile of 75 phospholipid species including quantification of the bioactive lysophosphatidylcholines (LPCs) was determined using liquid chromatography coupled to time-of-flight mass spectrometry. To control for possible enzymatic degradation of LPCs, serum autotaxin levels were examined. Twenty-two of the 33 patients with a clinical diagnosis of CAP received a laboratory-verified CAP diagnosis by microbial culture or microbial DNA detection by qPCR. All major phospholipid species, especially the LPCs, were pronouncedly decreased in the acute stage of illness. Total and individual LPC concentrations increased shortly after the initiation of antibiotic treatment, concentrations were at their lowest 3h after the initiation, and increased after Day 1. The total LPC concentration increased by a change ratio of 1.6–1.7 between acute illness and Day 2, and by a ratio of 3.7 between acute illness and full disease resolution. Autotaxin levels were low in acute illness and showed little changes over time, contradicting a hypothesis of enzymatic degradation causing the low levels of LPCs. In this sample of patients with CAP, the results demonstrate that LPC concentration changes in serum of patients with CAP closely mirrored the early transition from acute illness to recovery after the initiation of antibiotics. LPCs should be further explored as potential disease stage biomarkers in CAP and for their potential physiological role during recovery.

  • 47.
    Näsström, Elin
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Jonsson, Pär
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Dongol, Sabina
    Oxford University Clinical Research Unit, Patan Academy of Health Sciences, Kathmandu, Nepal.
    Karkey, Abhilasha
    Oxford University Clinical Research Unit, Patan Academy of Health Sciences, Kathmandu, Nepal.
    Basnyat, Buddha
    Oxford University Clinical Research Unit, Patan Academy of Health Sciences, Kathmandu, Nepal.
    Nga, Tran Vu Thieu
    The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University; Clinical Research Unit, Ho Chi Minh City, Vietnam.
    Tan, Trinh Van
    The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University; Clinical Research Unit, Ho Chi Minh City, Vietnam.
    Thwaites, Guy E
    The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University; Clinical Research Unit, Ho Chi Minh City, Vietnam. Centre for Tropical Medicine and Global Health, Oxford University, Oxford, United Kingdom.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Baker, Stephen
    The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University; Clinical Research Unit, Ho Chi Minh City, Vietnam. Centre for Tropical Medicine and Global Health, Oxford University, Oxford, United Kingdom. The Department of Medicine, The University of Cambridge, Cambridge, United Kingdom .
    Metabolite biomarkers of typhoid chronic carriageManuskript (preprint) (Övrigt vetenskapligt)
  • 48.
    Näsström, Elin
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Jonsson, Pär
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Dongol, Sabina
    Karkey, Abhilasha
    Basnyat, Buddha
    Thieu, Nga Tran Vu
    Van, Tan Trinh
    Thwaites, Guy E.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Baker, Stephen
    Diagnostic metabolite biomarkers of chronic typhoid carriage2018Ingår i: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 12, nr 1, artikel-id e0006215Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Salmonella Typhi and Salmonella Paratyphi A are the agents of enteric (typhoid) fever; both can establish chronic carriage in the gallbladder. Chronic Salmonella carriers are typically asymptomatic, intermittently shedding bacteria in the feces, and contributing to disease transmission. Detecting chronic carriers is of public health relevance in areas where enteric fever is endemic, but there are no routinely used methods for prospectively identifying those carrying Salmonella in their gallbladder.

    Methodology/Principal findings: Here we aimed to identify biomarkers of Salmonella carriage using metabolite profiling. We performed metabolite profiling on plasma from Nepali patients undergoing cholecystectomy with confirmed S. Typhi or S. Paratyphi A gallbladder carriage (and non-carriage controls) using two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS) and supervised pattern recognition modeling. We were able to significantly discriminate Salmonella carriage samples from non-carriage control samples. We were also able to detect differential signatures between S. Typhi and S. Paratyphi A carriers. We additionally compared carriage metabolite profiles with profiles generated during acute infection; these data revealed substantial heterogeneity between metabolites associated with acute enteric fever and chronic carriage. Lastly, we found that Salmonella carriers could be significantly distinguished from non-carriage controls using only five metabolites, indicating the potential of these metabolites as diagnostic markers for detecting chronic Salmonella carriers.

    Conclusions/Significance: Our novel approach has highlighted the potential of using metabolomics to search for diagnostic markers of chronic Salmonella carriage. We suggest further epidemiological investigations of these potential biomarkers in alternative endemic enteric fever settings.

  • 49.
    Näsström, Elin
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Parry, Christopher M.
    Thieu, Nga Tran Vu
    Maude, Rapeephan R.
    de Jong, Hanna K.
    Fukushima, Masako
    Rzhepishevska, Olena
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Marks, Florian
    Panzner, Ursula
    Im, Justin
    Jeon, Hyonjin
    Park, Seeun
    Chaudhury, Zabeen
    Ghose, Aniruddha
    Samad, Rasheda
    Van, Tan Trinh
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Dondorp, Arjen M.
    Thwaites, Guy E.
    Faiz, Abul
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Baker, Stephen
    Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa2017Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 6, artikel-id e15651Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Salmonella Typhi is the causative agent of typhoid. Typhoid is diagnosed by blood culture, a method that lacks sensitivity, portability and speed. We have previously shown that specific metabolomic profiles can be detected in the blood of typhoid patients from Nepal (Nasstrom et al., 2014). Here, we performed mass spectrometry on plasma from Bangladeshi and Senegalese patients with culture confirmed typhoid fever, clinically suspected typhoid, and other febrile diseases including malaria. After applying supervised pattern recognition modelling, we could significantly distinguish metabolite profiles in plasma from the culture confirmed typhoid patients. After comparing the direction of change and degree of multivariate significance, we identified 24 metabolites that were consistently up- or down regulated in a further Bangladeshi/Senegalese validation cohort, and the Nepali cohort from our previous work. We have identified and validated a metabolite panel that can distinguish typhoid from other febrile diseases, providing a new approach for typhoid diagnostics.

  • 50.
    Näsström, Elin
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Thieu, Nga Tran Vu
    Dongol, Sabina
    Karkey, Abhilasha
    Vinh, Phat Voong
    Thanh, Tuyen Ha
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Arjyal, Amit
    Thwaites, Guy
    Dolecek, Christiane
    Basnyat, Buddha
    Baker, Stephen
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Salmonella Typhi and Salmonella Paratyphi A elaborate distinct systemic metabolite signatures during enteric fever2014Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 3, artikel-id e03100Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The host-pathogen interactions induced by Salmonella Typhi and Salmonella Paratyphi A during enteric fever are poorly understood. This knowledge gap, and the human restricted nature of these bacteria, limit our understanding of the disease and impede the development of new diagnostic approaches. To investigate metabolite signals associated with enteric fever we performed two-dimensional gas chromatography with time-of-flight mass spectrometry (GCxGC/TOFMS) on plasma from patients with S. Typhi and S. Paratyphi A infections and asymptomatic controls, identifying 695 individual metabolite peaks. Applying supervised pattern recognition, we found highly significant and reproducible metabolite profiles separating S. Typhi cases, S. Paratyphi A cases, and controls, calculating that a combination of six metabolites could accurately define the etiological agent. For the first time we show that reproducible and serovar specific systemic biomarkers can be detected during enteric fever. Our work defines several biologically plausible metabolites that can be used to detect enteric fever, and unlocks the potential of this method in diagnosing other systemic bacterial infections.

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