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Johansson, Anders
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Dwibedi, C. K., Larsson, P., Ahlinder, J., Lindgren, P., Myrtennäs, K., Granberg, M., . . . Johansson, A. (2020). Biological amplification of low frequency mutations unravels laboratory culture history of the bio-threat agent Francisella tularensis. Forensic Science International: Genetics, 45
Åpne denne publikasjonen i ny fane eller vindu >>Biological amplification of low frequency mutations unravels laboratory culture history of the bio-threat agent Francisella tularensis
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2020 (engelsk)Inngår i: Forensic Science International: Genetics, ISSN 1872-4973, E-ISSN 1878-0326, Vol. 45Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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

sted, utgiver, år, opplag, sider
Elsevier, 2020
Emneord
Microbial forensics, Francisella tularensis, Molecular evolution, Genetic variation, Monomorphic bacteria, Source attribution
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-168168 (URN)10.1016/j.fsigen.2019.102230 (DOI)000508656600013 ()31924594 (PubMedID)
Tilgjengelig fra: 2020-03-17 Laget: 2020-03-17 Sist oppdatert: 2020-03-17bibliografisk kontrollert
Lindgren, P., Myrtennäs, K., Forsman, M., Johansson, A., Stenberg, P., Nordgaard, A. & Ahlinder, J. (2019). A likelihood ratio-based approach for improved source attribution in microbiological forensic investigations. Forensic Science International, 302, Article ID 109869.
Åpne denne publikasjonen i ny fane eller vindu >>A likelihood ratio-based approach for improved source attribution in microbiological forensic investigations
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2019 (engelsk)Inngår i: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 302, artikkel-id 109869Artikkel i tidsskrift (Fagfellevurdert) Published
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. 

sted, utgiver, år, opplag, sider
Elsevier, 2019
Emneord
Microbial source tracking, Bayes factor, Hypothesis assessment, Listeria monocytogenes, Francisella tularensis, Likelihood ratio
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-165758 (URN)10.1016/j.forsciint.2019.06.027 (DOI)000496801100024 ()31302416 (PubMedID)
Forskningsfinansiär
The Swedish Institute of International Affairs, A4952Swedish Armed Forces, A4040
Tilgjengelig fra: 2019-12-09 Laget: 2019-12-09 Sist oppdatert: 2019-12-09bibliografisk kontrollert
Müller, D. C., Kauppi, A., Edin, A., Gylfe, Å., Sjöstedt, A. B. & Johansson, A. (2019). Phospholipid Levels in Blood during Community-Acquired Pneumonia. PLoS ONE, 14(5), Article ID e0216379.
Åpne denne publikasjonen i ny fane eller vindu >>Phospholipid Levels in Blood during Community-Acquired Pneumonia
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2019 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, nr 5, artikkel-id e0216379Artikkel i tidsskrift (Fagfellevurdert) Published
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.

sted, utgiver, år, opplag, sider
Public Library of Science, 2019
Emneord
Community-acquired pneumonia, phospholipids, infection, diagnosis, metabolomics
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-147058 (URN)10.1371/journal.pone.0216379 (DOI)000467148400025 ()31063483 (PubMedID)
Merknad

Originally included in thesis in manuscript form 

Tilgjengelig fra: 2018-04-25 Laget: 2018-04-25 Sist oppdatert: 2019-06-12bibliografisk kontrollert
Hosseinzadeh, A., Stylianou, M., Lopes, J. P., Müller, D. C., Häggman, A., Holmberg, S., . . . Urban, C. F. (2019). Stable Redox-Cycling Nitroxide Tempol has Antifungal and Immune-modulatory Properties. Frontiers in Microbiology, 10, Article ID 1843.
Åpne denne publikasjonen i ny fane eller vindu >>Stable Redox-Cycling Nitroxide Tempol has Antifungal and Immune-modulatory Properties
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2019 (engelsk)Inngår i: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 10, artikkel-id 1843Artikkel i tidsskrift (Fagfellevurdert) Published
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.

Emneord
antifungal activity, redox active, immunomodulators, candidiasis, Candida albicans, Candida glabrata
HSV kategori
Forskningsprogram
infektionssjukdomar
Identifikatorer
urn:nbn:se:umu:diva-151596 (URN)10.3389/fmicb.2019.01843 (DOI)000481763300001 ()31481939 (PubMedID)
Forskningsfinansiär
Swedish Research Council, 2014-02281The Kempe Foundations, 1453
Merknad

Originally included in thesis in manuscript form 

Tilgjengelig fra: 2018-09-07 Laget: 2018-09-07 Sist oppdatert: 2019-10-11bibliografisk kontrollert
Birdsell, D. N., Özsürekci, Y., Rawat, A., Aycan, A. E., Mitchell, C. L., Sahl, J. W., . . . Wagner, D. M. (2018). Coinfections identified from metagenomic analysis of cervical lymph nodes from tularemia patients. BMC Infectious Diseases, 18, Article ID 319.
Åpne denne publikasjonen i ny fane eller vindu >>Coinfections identified from metagenomic analysis of cervical lymph nodes from tularemia patients
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2018 (engelsk)Inngår i: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 18, artikkel-id 319Artikkel i tidsskrift (Fagfellevurdert) Published
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.

sted, utgiver, år, opplag, sider
BMC, 2018
Emneord
Coinfections, Concurrent infections, Tularemia, Francisella tularensis, Metagenomics, Fine-needle lymph node aspirate
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-150725 (URN)10.1186/s12879-018-3218-2 (DOI)000438284500003 ()29996780 (PubMedID)2-s2.0-85049848852 (Scopus ID)
Tilgjengelig fra: 2018-08-29 Laget: 2018-08-29 Sist oppdatert: 2018-08-29bibliografisk kontrollert
Näsström, E., Jonsson, P., Johansson, A., Dongol, S., Karkey, A., Basnyat, B., . . . Baker, S. (2018). Diagnostic metabolite biomarkers of chronic typhoid carriage. PLoS Neglected Tropical Diseases, 12(1), Article ID e0006215.
Åpne denne publikasjonen i ny fane eller vindu >>Diagnostic metabolite biomarkers of chronic typhoid carriage
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2018 (engelsk)Inngår i: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 12, nr 1, artikkel-id e0006215Artikkel i tidsskrift (Fagfellevurdert) Published
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.

HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-145618 (URN)10.1371/journal.pntd.0006215 (DOI)000424022700063 ()29373578 (PubMedID)
Forskningsfinansiär
Swedish Research Council, VR-U 2015-03442
Tilgjengelig fra: 2018-04-17 Laget: 2018-04-17 Sist oppdatert: 2018-06-09bibliografisk kontrollert
Mostafavi, E., Ghasemi, A., Rohani, M., Molaeipoor, L., Esmaeili, S., Mohammadi, Z., . . . Johansson, A. (2018). Molecular Survey of Tularemia and Plague in Small Mammals From Iran. Frontiers in Cellular and Infection Microbiology, 8, Article ID 215.
Åpne denne publikasjonen i ny fane eller vindu >>Molecular Survey of Tularemia and Plague in Small Mammals From Iran
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2018 (engelsk)Inngår i: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 8, artikkel-id 215Artikkel i tidsskrift (Fagfellevurdert) Published
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.

sted, utgiver, år, opplag, sider
Frontiers Media S.A., 2018
Emneord
tularemia, plague, hares, rodentia, insectivora
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-150726 (URN)10.3389/fcimb.2018.00215 (DOI)000438132600001 ()30042927 (PubMedID)2-s2.0-85049947197 (Scopus ID)
Tilgjengelig fra: 2018-08-29 Laget: 2018-08-29 Sist oppdatert: 2018-08-29bibliografisk kontrollert
Näsström, E., Parry, C. M., Thieu, N. T., Maude, R. R., de Jong, H. K., Fukushima, M., . . . Baker, S. (2017). Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa. eLIFE, 6, Article ID e15651.
Åpne denne publikasjonen i ny fane eller vindu >>Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa
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2017 (engelsk)Inngår i: eLIFE, E-ISSN 2050-084X, Vol. 6, artikkel-id e15651Artikkel i tidsskrift (Fagfellevurdert) Published
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.

sted, utgiver, år, opplag, sider
eLife Sciences Publications, 2017
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-135532 (URN)10.7554/eLife.15651 (DOI)000400828100001 ()
Tilgjengelig fra: 2017-06-13 Laget: 2017-06-13 Sist oppdatert: 2018-06-09bibliografisk kontrollert
Forsell, J., Bengtsson-Palme, J., Angelin, M., Johansson, A., Evengård, B. & Granlund, M. (2017). The relation between Blastocystis and the intestinal microbiota in Swedish travellers. BMC Microbiology, 17, Article ID 231.
Åpne denne publikasjonen i ny fane eller vindu >>The relation between Blastocystis and the intestinal microbiota in Swedish travellers
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2017 (engelsk)Inngår i: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 17, artikkel-id 231Artikkel i tidsskrift (Fagfellevurdert) Published
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.

Emneord
Blastocystis; subtype; persistence; travel; microbiota; Sporolactobacillus; Candidatus Carsonella; transmission
HSV kategori
Forskningsprogram
klinisk bakteriologi
Identifikatorer
urn:nbn:se:umu:diva-132437 (URN)10.1186/s12866-017-1139-7 (DOI)000418138200001 ()29228901 (PubMedID)
Merknad

Originally included in thesis in manuscript form

Tilgjengelig fra: 2017-03-14 Laget: 2017-03-14 Sist oppdatert: 2018-06-09bibliografisk kontrollert
Karlsson, E., Golovliov, I., Lärkeryd, A., Granberg, M., Larsson, E., Öhrman, C., . . . Johansson, A. (2016). Clonality of erythromycin resistance in Francisella tularensis. Journal of Antimicrobial Chemotherapy, 71(10), 2815-2823
Åpne denne publikasjonen i ny fane eller vindu >>Clonality of erythromycin resistance in Francisella tularensis
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2016 (engelsk)Inngår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, nr 10, s. 2815-2823Artikkel i tidsskrift (Fagfellevurdert) Published
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.

HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-130064 (URN)10.1093/jac/dkw235 (DOI)000386453900016 ()27334667 (PubMedID)
Tilgjengelig fra: 2017-01-13 Laget: 2017-01-11 Sist oppdatert: 2018-06-09bibliografisk kontrollert
Organisasjoner