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  • 1.
    Bergqvist, Joakim
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Forsman, Oscar
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Larsson, Pär
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Näslund, Jonas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Lilja, Tobias
    Engdahl, Cecilia
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lindström, Anders
    Gylfe, Åsa
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Arctic Research Centre at Umeå University.
    Bucht, Göran
    [ 1 ] CBRN Def & Secur, Swedish Def Res Agcy, SE-90182 Umea, Sweden.
    Detection and Isolation of Sindbis Virus from Mosquitoes Captured During an Outbreak in Sweden, 20132015In: Vector Borne and Zoonotic Diseases, ISSN 1530-3667, E-ISSN 1557-7759, Vol. 15, no 2, p. 133-140Article in journal (Refereed)
    Abstract [en]

    Mosquito-borne alphaviruses have the potential to cause large outbreaks throughout the world. Here we investigated the causative agent of an unexpected Sindbis virus (SINV) outbreak during August-September, 2013, in a previously nonendemic region of Sweden. Mosquitoes were collected using carbon dioxide-baited CDC traps at locations close to human cases. The mosquitoes were initially screened as large pools by SINV-specific quantitative RT-PCR, and the SINV-positive mosquitoes were species determined by single-nucleotide polymorphism (SNP) analysis, followed by sequencing the barcoding region of the cytochrome oxidase I gene. The proportion of the collected mosquitoes was determined by a metabarcoding strategy. By using novel strategies for PCR screening and genetic typing, a new SINV strain, Lovanger, was isolated from a pool of 1600 mosquitoes composed of Culex, Culiseta, and Aedes mosquitoes as determined by metabarcoding. The SINV-positive mosquito Culiseta morsitans was identified by SNP analysis and sequencing. After whole-genome sequencing and phylogenetic analysis, the SINV Lovanger isolate was shown to be most closely similar to recent Finnish SINV isolates. In conclusion, within a few weeks, we were able to detect and isolate a novel SINV strain and identify the mosquito vector during a sudden SINV outbreak.

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

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

  • 3.
    Borssén, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nordlund, Jessica
    Haider, Zahra
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Landfors, Mattias
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Larsson, Pär
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Kanerva, Jukka
    Schmiegelow, Kjeld
    Flaegstad, Trond
    Jónsson, Ólafur Gísli
    Frost, Britt-Marie
    Palle, Josefine
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Heyman, Mats
    Hultdin, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lönnerholm, Gudmar
    Degerman, Sofie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    DNA methylation holds prognostic information in relapsed precursor B-cell acute lymphoblastic leukemia2018In: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 10, article id 31Article in journal (Refereed)
    Abstract [en]

    Background: Few biological markers are associated with survival after relapse of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In pediatric T-cell ALL, we have identified promoter-associated methylation alterations that correlate with prognosis. Here, the prognostic relevance of CpG island methylation phenotype (CIMP) classification was investigated in pediatric BCP-ALL patients.

    Methods: Six hundred and one BCP-ALL samples from Nordic pediatric patients (age 1-18) were CIMP classified at initial diagnosis and analyzed in relation to clinical data.

    Results: Among the 137 patients that later relapsed, patients with a CIMP-profile (n = 42) at initial diagnosis had an inferior overall survival (pOS(5years) 33%) compared to CIMP+ patients (n = 95, pOS(5years) 65%) (p = 0.001), which remained significant in a Cox proportional hazards model including previously defined risk factors.

    Conclusion: CIMP classification is a strong candidate for improved risk stratification of relapsed BCP-ALL.

  • 4.
    Eklöf, Vincy
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Löfgren-Burström, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Zingmark, Carl
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Edin, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Larsson, Pär
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Alexeyev, Oleg
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Rutegård, Jörgen
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Wikberg, Maria L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Cancer-associated fecal microbial markers in colorectal cancer detection2017In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 141, no 12, p. 2528-2536Article in journal (Refereed)
    Abstract [en]

    Colorectal cancer (CRC) is the second most common cause of cancer death in the western world. An effective screening program leading to early detection of disease would severely reduce the mortality of CRC. Alterations in the gut microbiota have been linked to CRC, but the potential of microbial markers for use in CRC screening has been largely unstudied. We used a nested case-control study of 238 study subjects to explore the use of microbial markers for clbA+ bacteria harboring the pks pathogenicity island, afa-C+ diffusely adherent Escherichia coli harboring the afa-1 operon, and Fusobacterium nucleatum in stool as potential screening markers for CRC. We found that individual markers for clbA+ bacteria and F. nucleatum were more abundant in stool of patients with CRC, and could predict cancer with a relatively high specificity (81.5% and 76.9%, respectively) and with a sensitivity of 56.4% and 69.2%, respectively. In a combined test of clbA+ bacteria and F. nucleatum, CRC was detected with a specificity of 63.1% and a sensitivity of 84.6%. Our findings support a potential value of microbial factors in stool as putative noninvasive biomarkers for CRC detection. We propose that microbial markers may represent an important future screening strategy for CRC, selecting patients with a "high-risk" microbial pattern to other further diagnostic procedures such as colonoscopy.

  • 5.
    Haider, Zahra
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Larsson, Pär
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Landfors, Mattias
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Köhn, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Schmiegelow, Kjeld
    Flaegstad, Trond
    Kanerva, Jukka
    Heyman, Mats
    Hultdin, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Degerman, Sofie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    An integrated transcriptome analysis in T-cell acute lymphoblastic leukemia links DNA methylation subgroups to dysregulated TAL1 and ANTP homeobox gene expression2019In: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 8, no 1, p. 311-324Article in journal (Refereed)
    Abstract [en]

    Classification of pediatric T‐cell acute lymphoblastic leukemia (T‐ALL) patients into CIMP (CpG Island Methylator Phenotype) subgroups has the potential to improve current risk stratification. To investigate the biology behind these CIMP subgroups, diagnostic samples from Nordic pediatric T‐ALL patients were characterized by genome‐wide methylation arrays, followed by targeted exome sequencing, telomere length measurement, and RNA sequencing. The CIMP subgroups did not correlate significantly with variations in epigenetic regulators. However, the CIMP+ subgroup, associated with better prognosis, showed indicators of longer replicative history, including shorter telomere length (P = 0.015) and older epigenetic (P < 0.001) and mitotic age (P < 0.001). Moreover, the CIMP+ subgroup had significantly higher expression of ANTP homeobox oncogenes, namely TLX3, HOXA9, HOXA10, and NKX2‐1, and novel genes in T‐ALL biology including PLCB4, PLXND1, and MYO18B. The CIMP− subgroup, with worse prognosis, was associated with higher expression of TAL1 along with frequent STIL‐TAL1 fusions (2/40 in CIMP+ vs 11/24 in CIMP−), as well as stronger expression of BEX1. Altogether, our findings suggest different routes for leukemogenic transformation in the T‐ALL CIMP subgroups, indicated by different replicative histories and distinct methylomic and transcriptomic profiles. These novel findings can lead to new therapeutic strategies.

  • 6. Havlasová, Jana
    et al.
    Hernychová, Lenka
    Brychta, Martin
    Hubálek, Martin
    Lenco, Jurai
    Larsson, Pär
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Swedish Defence Research Agency, Umeå, Sweden.
    Lundqvist, Margaretha
    Swedish Defence Research Agency, Umeå, Sweden.
    Forsman, Mats
    Swedish Defence Research Agency, Umeå, Sweden.
    Kročová, Zulana
    Stulík, Jiri
    Macela, Aks
    Proteomic analysis of anti-Franciselia tularensis LVS antibody response in murine model of tularemia2005In: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 5, no 8, p. 2090-2103Article in journal (Refereed)
    Abstract [en]

    Francisella tularensis live vaccine strain infection of mice has been established as an experimental model of tularemia that is suitable for studies of immune mechanisms against the intracellular pathogen. In this study, the model was used to explore immunogenic repertoire of F. tularensis with the aim of identifying new molecules able to activate the host immune system, potential bacterial markers with vaccine, and diagnostic applications. Immunoproteomic approach based on the combination of two-dimensional gel electrophoresis, immunoblotting, and mass spectrometry was applied. Globally, 36 different proteins were identified, which strongly reacted with sera from experimentally infected mice, including several putative virulence markers of intracellular pathogens as nucleoside diphosphate kinase, isocitrate dehydrogenase, RNA-binding protein Hfq, and molecular chaperone ClpB. Of them, 27 proteins are described for the first time as immunorelevant Francisella proteins. When comparing murine immunoproteome of F. tularensis with our previous data from human patients, 25 of the total of 50 identified murine sera immunoreactive spots were recognized by human sera collected from patients suffering from tularemia, as well. Immune sera from two Lps gene congenic strains of mice, C3H/HeN (Lpsn) and C3H/HeJ (Lpsd), represented murine immunoproteome in this study. The spectrum of immunoreactive spots detected by two-dimensional immunoblotting varied throughout the course of infection depending on murine strain. Nevertheless, the antibody patterns of the two strains showed significant homogeneity in being directed against almost identical subset of antigens.

  • 7.
    Johansson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Celli, Jean
    Conlan, Wayne
    NRC, Canada.
    Elkins, Karen L
    Forsman, Mats
    Swedish Defense Research Agency, Umea, Sweden.
    Keim, Paul S
    Larsson, Pär
    Swedish Defense Research Agency, Umea, Sweden.
    Manoil, Colin
    Nano, Francis E
    Petersen, Jeannine M
    Sjöstedt, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Objections to the transfer of Francisella novicida to the subspecies rank of Francisella tularensis2010In: International Journal of Systematic and Evolutionary Microbiology, ISSN 1466-5026, E-ISSN 1466-5034, Vol. 60, no 8, p. 1717-1718Article in journal (Refereed)
  • 8.
    Larsson, Pär
    et al.
    Swedish Defense Research Agency, Umeå, Sweden.
    Elfsmark, Daniel
    Swedish Defense Research Agency, Umeå, Sweden.
    Svensson, Kerstin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Wikström, Per
    Swedish Defense Research Agency, Umeå, Sweden.
    Forsman, Mats
    Swedish Defense Research Agency, Umeå, Sweden.
    Brettin, Thomas
    Keim, Paul
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Molecular evolutionary consequences of niche restriction in Francisella tularensis, a facultative intracellular pathogen2009In: PLoS pathogens, ISSN 1553-7374, Vol. 5, no 6, p. e1000472-Article in journal (Refereed)
    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.

  • 9.
    Ling, Agnes
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Löfgren-Burström, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Larsson, Pär
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Li, Xingru
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wikberg, Maria L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Öberg, Åke
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Stenling, Roger
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Edin, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    TAP1 down-regulation elicits immune escape and poor prognosis in colorectal cancer2017In: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 6, no 11, article id e1356143Article in journal (Refereed)
    Abstract [en]

    The anti-tumor immune response has been shown to be of great prognostic importance in colorectal cancer (CRC) and so has the tumors ability for immune evasion. Our aim of this study was to investigate tumor factors that influence immunity. We used a gene expression array to search for potential mechanisms of tumor immune escape. One candidate gene identified was TAP1, involved in antigen presentation by MHC class I. TAP1 protein expression was evaluated by immunohistochemistry in 436 CRC patients of the Colorectal Cancer in Umeå Study cohort. We found a significant association between a downregulated expression of TAP1 and low infiltration of various subtypes of lymphocytes as well as macrophages. A downregulated expression of TAP1 was further found to be independent of molecular characteristics, suggesting TAP1 down-regulation to reach beyond the well described highly immunogenic MSI CRCs. A low expression of TAP1 was also significantly associated with poor prognosis in patients with CRC, a result that stayed significant in tumor front of early stage tumors (stage I-II) through multivariable analyses. Furthermore, we found that TAP1 expression was inversely correlated with methylation at sites in close proximity to the promoter region. In summary, our results show down-regulation of TAP1 to be a general mechanism of tumor immune escape in CRC and a poor prognostic factor in stage I-II CRC patients. We also suggest that methylation of the TAP1 gene may be a putative mechanism for TAP1 downregulation.

  • 10.
    Myrtennäs, Kerstin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. FOI.
    Sjödin, Andreas
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    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 University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Genome sequence of Francisella Tularensis subspecies holarctica Strain FSC200, isolated from a child with Tularemia2012In: Journal of Bacteriology, ISSN 0021-9193, E-ISSN 1098-5530, Vol. 194, no 24, p. 6965-6966Article in journal (Refereed)
    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.

  • 11.
    Norberg, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Rosén, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Raaschou-Jensen, Klas
    Kjeldsen, Lars
    Moilanen, Jukka S.
    Paulsson-Karisson, Ylva
    Baliakas, Panagiotis
    Lohi, Olli
    Ahmed, Aymen
    Kittang, Astrid O.
    Larsson, Pär
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Roos, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Degerman, Sofie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hultdin, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Novel variants in Nordic patients referred for genetic testing of telomere-related disorders2018In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 26, no 6, p. 858-867Article in journal (Refereed)
    Abstract [en]

    Telomere-related disorders are a clinically and genetically heterogeneous group of disorders characterized by premature telomere shortening and proliferative failure of a variety of tissues. This study reports the spectrum of telomere-related gene variants and telomere length in Nordic patients referred for genetic testing due to suspected telomere-related disorder. We performed Sanger sequencing of the genes TERT, TERC, DKC1, and TINF2 on 135 unrelated index patients and measured telomere length by qPCR on DNA from peripheral blood leukocytes. We identified pathogenic or likely pathogenic variants in 10 index patients, all of which had short telomeres compared to age-matched healthy controls. Six of the 10 variants were novel; three in TERC (n.69_74dupAGGCGC, n.122_125delGCGG, and n.407_408delinsAA) and three in TERT (p.(D684G), p.(R774*), and p.(*1133Wext*39)). The high proportion of novel variants identified in our study highlights the need for solid interpretation of new variants that may be detected. Measurement of telomere length is a useful approach for evaluating pathogenicity of genetic variants associated with telomere-related disorders.

  • 12. Sjödin, Andreas
    et al.
    Svensson, Kerstin
    FOI.
    Öhrman, Caroline
    Ahlinder, Jon
    Lindgren, Petter
    Duodu, Samuel
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Colquhoun, Duncan J.
    Larsson, Pär
    Swedish Defense Research Agency, Umea, Sweden.
    Forsman, Mats
    Genome characterisation of the genus Francisella reveals insight into similar evolutionary paths in pathogens of mammals and fish2012In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 13, p. 268-Article in journal (Refereed)
    Abstract [en]

    Background: Prior to this study, relatively few strains of Francisella had been genome-sequenced. Previously published Francisella genome sequences were largely restricted to the zoonotic agent F. tularensis. Only limited data were available for other members of the Francisella genus, including F. philomiragia, an opportunistic pathogen of humans, F. noatunensis, a serious pathogen of farmed fish, and other less well described endosymbiotic species. Results: We determined the phylogenetic relationships of all known Francisella species, including some for which the phylogenetic positions were previously uncertain. The genus Francisella could be divided into two main genetic clades: one included F. tularensis, F. novicida, F. hispaniensis and Wolbachia persica, and another included F. philomiragia and F. noatunensis. Some Francisella species were found to have significant recombination frequencies. However, the fish pathogen F. noatunensis subsp. noatunensis was an exception due to it exhibiting a highly clonal population structure similar to the human pathogen F. tularensis. Conclusions: The genus Francisella can be divided into two main genetic clades occupying both terrestrial and marine habitats. However, our analyses suggest that the ancestral Francisella species originated in a marine habitat. The observed genome to genome variation in gene content and IS elements of different species supports the view that similar evolutionary paths of host adaptation developed independently in F. tularensis (infecting mammals) and F. noatunensis subsp. noatunensis (infecting fish).

  • 13.
    Svensson, Kerstin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Bäck, Erik
    Örebro universitet.
    Berglund, Lennart
    Eliasson, Henrik
    Granberg, M
    Karlsson, Lena
    Larsson, Pär
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Forsman, Mats
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    A high-resolution landscape epidemiology of tularemia exposed by genetic analysis of the causative agent isolated from infected humansManuscript (Other academic)
  • 14.
    Svensson, Kerstin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Bäck, Erik
    Örebro Universitetssjukhus.
    Eliasson, Henrik
    Örebro Universitetssjukhus.
    Berglund, Lennart
    Granberg, Malin
    Karlsson, Linda
    Swedish Defense Research Agency, Umea, Sweden.
    Larsson, Pär
    Swedish Defense Research Agency, Umea, Sweden.
    Forsman, Mats
    Swedish Defense Research Agency, Umea, Sweden.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Landscape epidemiology of tularemia outbreaks in Sweden2009In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 15, no 12, p. 1937-1947Article in journal (Refereed)
    Abstract [en]

    Summer outbreaks of tularemia that occurred from 1995 through 2005 in 2 locations in Sweden affected 441 persons. We performed an epidemiologic investigation of these outbreaks using a novel strategy, involving high-resolution genotyping of Francisella tularensis isolates obtained from 136 patients (using 18 genetic markers developed from 6 F. tularensis genome sequences) and interviews with the patients. Strong spatial associations were found between F. tularensis subpopulations and the places of disease transmission; infection by some subpopulations occurred within areas as small as 2 km(2), indicating unidentified environmental point sources of tularemia. In both locations, disease clusters were associated with recreational areas beside water, and genetic subpopulations were present throughout the tularemia season and persisted over years. High-resolution genotyping in combination with patients' statements about geographic places of disease transmission provided valuable indications of likely sources of infection and the causal genotypes during these tularemia outbreaks.

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