| 1. |
- Vogler, Amy J, et al.
(author)
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Phylogeography of Francisella tularensis : global expansion of a highly fit clone
- 2009
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In: Journal of Bacteriology. - : American Society for Microbiology. - 0021-9193 .- 1098-5530. ; 191:8, s. 2474-2484
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Journal article (peer-reviewed)abstract
- Francisella tularensis contains several highly pathogenic subspecies, including Francisella tularensis subsp. holarctica, whose distribution is circumpolar in the northern hemisphere. The phylogeography of these subspecies and their subclades was examined using whole-genome single nucleotide polymorphism (SNP) analysis, high-density microarray SNP genotyping, and real-time-PCR-based canonical SNP (canSNP) assays. Almost 30,000 SNPs were identified among 13 whole genomes for phylogenetic analysis. We selected 1,655 SNPs to genotype 95 isolates on a high-density microarray platform. Finally, 23 clade- and subclade-specific canSNPs were identified and used to genotype 496 isolates to establish global geographic genetic patterns. We confirm previous findings concerning the four subspecies and two Francisella tularensis subsp. tularensis subpopulations and identify additional structure within these groups. We identify 11 subclades within F. tularensis subsp. holarctica, including a new, genetically distinct subclade that appears intermediate between Japanese F. tularensis subsp. holarctica isolates and the common F. tularensis subsp. holarctica isolates associated with the radiation event (the B radiation) wherein this subspecies spread throughout the northern hemisphere. Phylogenetic analyses suggest a North American origin for this B-radiation clade and multiple dispersal events between North America and Eurasia. These findings indicate a complex transmission history for F. tularensis subsp. holarctica.
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| 2. |
- Birdsell, Dawn N, et al.
(author)
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Francisella tularensis subsp. tularensis group A.I, United States
- 2014
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In: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 20:5, s. 861-865
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Journal article (peer-reviewed)abstract
- 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.
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| 3. |
- Champion, Mia D, et al.
(author)
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Comparative genomic characterization of Francisella tularensis strains belonging to low and high virulence subspecies
- 2009
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In: PLoS pathogens. - : Public Library of Science (PLoS). - 1553-7374. ; 5:5, s. e1000459-
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Journal article (peer-reviewed)abstract
- Tularemia is a geographically widespread, severely debilitating, and occasionally lethal disease in humans. It is caused by infection by a gram-negative bacterium, Francisella tularensis. In order to better understand its potency as an etiological agent as well as its potential as a biological weapon, we have completed draft assemblies and report the first complete genomic characterization of five strains belonging to the following different Francisella subspecies (subsp.): the F. tularensis subsp. tularensis FSC033, F. tularensis subsp. holarctica FSC257 and FSC022, and F. tularensis subsp. novicida GA99-3548 and GA99-3549 strains. Here, we report the sequencing of these strains and comparative genomic analysis with recently available public Francisella sequences, including the rare F. tularensis subsp. mediasiatica FSC147 strain isolate from the Central Asian Region. We report evidence for the occurrence of large-scale rearrangement events in strains of the holarctica subspecies, supporting previous proposals that further phylogenetic subdivisions of the Type B clade are likely. We also find a significant enrichment of disrupted or absent ORFs proximal to predicted breakpoints in the FSC022 strain, including a genetic component of the Type I restriction-modification defense system. Many of the pseudogenes identified are also disrupted in the closely related rarely human pathogenic F. tularensis subsp. mediasiatica FSC147 strain, including modulator of drug activity B (mdaB) (FTT0961), which encodes a known NADPH quinone reductase involved in oxidative stress resistance. We have also identified genes exhibiting sequence similarity to effectors of the Type III (T3SS) and components of the Type IV secretion systems (T4SS). One of the genes, msrA2 (FTT1797c), is disrupted in F. tularensis subsp. mediasiatica and has recently been shown to mediate bacterial pathogen survival in host organisms. Our findings suggest that in addition to the duplication of the Francisella Pathogenicity Island, and acquisition of individual loci, adaptation by gene loss in the more recently emerged tularensis, holarctica, and mediasiatica subspecies occurred and was distinct from evolutionary events that differentiated these subspecies, and the novicida subspecies, from a common ancestor. Our findings are applicable to future studies focused on variations in Francisella subspecies pathogenesis, and of broader interest to studies of genomic pathoadaptation in bacteria.
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| 4. |
- Dwibedi, Chinmay Kumar, et al.
(author)
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Long-range dispersal moved Francisella tularensis into Western Europe from the East
- 2016
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In: Microbial Genomics. - : Microbiology Society. - 2057-5858. ; 2:12
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Journal article (peer-reviewed)abstract
- For many infections transmitting to humans from reservoirs in nature, disease dispersal patterns over space and time are largely unknown. Here, a reversed genomics approach helped us understand disease dispersal and yielded insight into evolution and biological properties of Francisella tularensis, the bacterium causing tularemia. We whole-genome sequenced 67 strains and characterized by single-nucleotide polymorphism assays 138 strains, collected from individuals infected 1947-2012 across Western Europe. We used the data for phylogenetic, population genetic and geographical network analyses. All strains (n= 205) belonged to a monophyletic population of recent ancestry not found outside Western Europe. Most strains (n= 195) throughout the study area were assigned to a star-like phylogenetic pattern indicating that colonization of Western Europe occurred via clonal expansion. In the East of the study area, strains were more diverse, consistent with a founder population spreading from east to west. The relationship of genetic and geographic distance within the F. tularensis population was complex and indicated multiple long-distance dispersal events. Mutation rate estimates based on year of isolation indicated null rates; in outbreak hotspots only, there was a rate of 0.4 mutations/genome/year. Patterns of nucleotide substitution showed marked AT mutational bias suggestive of genetic drift. These results demonstrate that tularemia has moved from east to west in Europe and that F. tularensis has a biology characterized by long-range geographical dispersal events and mostly slow, but variable, replication rates. The results indicate that mutation-driven evolution, a resting survival phase, genetic drift and long-distance geographical dispersal events have interacted to generate genetic diversity within this species.
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| 5. |
- Gyuranecz, Miklos, et al.
(author)
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Phylogeography of Francisella tularensis subsp holarctica, Europe
- 2012
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In: Emerging Infectious Diseases. - Atlanta : Centers Disease Control. - 1080-6040 .- 1080-6059. ; 18:2, s. 290-293
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Journal article (peer-reviewed)abstract
- 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.
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| 6. |
- Johansson, Anders, et al.
(author)
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An outbreak of respiratory tularemia caused by diverse clones of Francisella tularensis
- 2014
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In: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 59:11, s. 1546-53
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Journal article (peer-reviewed)abstract
- 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.
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| 7. |
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| 8. |
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| 9. |
- Keim, Paul, et al.
(author)
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Molecular epidemiology, evolution, and ecology of Francisella.
- 2007
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In: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1105, s. 30-66
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Journal article (peer-reviewed)abstract
- Tularemia is a disease caused by several subspecies of Francisella tularensis, although the severity of the disease varies greatly from subspecies to subspecies. Currently, there are four recognized subspecies (tularensis, holarctica, mediasiatica, and novicida), in addition to a second Francisella species, F. philomiragia. It is clear from molecular sampling of the environment that these human pathogens are a mere fraction of the Francisella diversity. Taxonomic nomenclature is now being based upon several DNA-sequence-based approaches and this advance provides for robust phylogenetic models that are guiding the systematics of this genus. This in turn allows for better molecular epidemiological investigations and more precise ecological analysis. Tularemia ecology is still only partially understood, with many knowledge gaps about the disease reservoir and vectors. Molecular analysis has identified a major population split within F. tularensis subsp. tularensis that points toward distinctive ecological adaptations, vectors, and host species. Current medical practice does not rely upon subspecies or subpopulation identification, although this information may have predictive value for clinical outcome, especially in the United States. Combined molecular and epidemiological analyses suggest that the population split in F. tularensis subsp. tularensis matches two distinct human diseases in the United States with different mortality rates. DNA-sequence-based typing of F. tularensis subsp. holarctica from tularemia outbreaks in Europe and the United States proves regional identity among isolates and also demonstrates that this subspecies successfully disseminated worldwide in recent evolutionary time.
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| 10. |
- Larsson, Pär, et al.
(author)
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Molecular evolutionary consequences of niche restriction in Francisella tularensis, a facultative intracellular pathogen
- 2009
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In: PLoS pathogens. - : Public Library of Science (PLoS). - 1553-7374. ; 5:6, s. e1000472-
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Journal article (peer-reviewed)abstract
- 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.
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| 11. |
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| 12. |
- Sutherland, William J., et al.
(author)
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A horizon scan of global conservation issues for 2014
- 2014
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In: Trends in Ecology & Evolution. - London : Elsevier. - 0169-5347 .- 1872-8383. ; 29:1, s. 15-22
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Research review (peer-reviewed)abstract
- This paper presents the output of our fifth annual horizon-scanning exercise, which aims to identify topics that increasingly may affect conservation of biological diversity, but have yet to be widely considered. A team of professional horizon scanners, researchers, practitioners, and a journalist identified 15 topics which were identified via an iterative, Delphi-like process. The 15 topics include a carbon market induced financial crash, rapid geographic expansion of macroalgal cultivation, genetic control of invasive species, probiotic therapy for amphibians, and an emerging snake fungal disease.
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| 13. |
- Sutherland, William J., et al.
(author)
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A Horizon Scan of Global Conservation Issues for 2016
- 2016
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In: Trends in Ecology & Evolution. - : Elsevier BV. - 0169-5347 .- 1872-8383. ; 31:1, s. 44-53
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Research review (peer-reviewed)abstract
- This paper presents the results of our seventh annual horizon scan, in which we aimed to identify issues that could have substantial effects on global biological diversity in the future, but are not currently widely well known or understood within the conservation community. Fifteen issues were identified by a team that included researchers, practitioners, professional horizon scanners, and journalists. The topics include use of managed bees as transporters of biological control agents, artificial superintelligence, electric pulse trawling, testosterone in the aquatic environment, building artificial oceanic islands, and the incorporation of ecological civilization principles into government policies in China.
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| 14. |
- Wagner, David M., et al.
(author)
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Genomic characterization of Francisella tularensis and other diverse Francisella species from complex samples
- 2022
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:10
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Journal article (peer-reviewed)abstract
- Francisella tularensis, the bacterium that causes the zoonosis tularemia, and its genetic near neighbor species, can be difficult or impossible to cultivate from complex samples. Thus, there is a lack of genomic information for these species that has, among other things, limited the development of robust detection assays for F. tularensis that are both specific and sensitive. The objective of this study was to develop and validate approaches to capture, enrich, sequence, and analyze Francisella DNA present in DNA extracts generated from complex samples. RNA capture probes were designed based upon the known pan genome of F. tularensis and other diverse species in the family Francisellaceae. Probes that targeted genomic regions also present in non-Francisellaceae species were excluded, and probes specific to particular Francisella species or phylogenetic clades were identified. The capture-enrichment system was then applied to diverse, complex DNA extracts containing low-level Francisella DNA, including human clinical tularemia samples, environmental samples (i.e., animal tissue and air filters), and whole ticks/tick cell lines, which was followed by sequencing of the enriched samples. Analysis of the resulting data facilitated rigorous and unambiguous confirmation of the detection of F. tularensis or other Francisella species in complex samples, identification of mixtures of different Francisella species in the same sample, analysis of gene content (e.g., known virulence and antimicrobial resistance loci), and high-resolution whole genome-based genotyping. The benefits of this capture-enrichment system include: even very low target DNA can be amplified; it is culture-independent, reducing exposure for research and/or clinical personnel and allowing genomic information to be obtained from samples that do not yield isolates; and the resulting comprehensive data not only provide robust means to confirm the presence of a target species in a sample, but also can provide data useful for source attribution, which is important from a genomic epidemiology perspective.
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| 15. |
- Zaccai, Nathan R., et al.
(author)
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Crystallographic and in silico analysis of the sialoside-binding characteristics of the Siglec sialoadhesin
- 2007
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In: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 365:5, s. 1469-1479
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Journal article (peer-reviewed)abstract
- The Siglec family of receptors mediates cell-surface interactions through recognition of sialylated glycoconjugates. Previously reported structures of the N-terminal domain of the Siglec sialoadhesin (SnD1) in complex with various sialic acid analogs revealed the structural template for sialic acid binding. To characterize further the carbohydrate-binding properties, we have determined the crystal structures of SnD1 in the absence of ligand, and in complex with 2-benzyl-Neu5NPro and 2-benzyl-Neu5NAc. These structures reveal that SnD1 undergoes very few structural changes on ligand binding and detail how two novel classes of sialic acid analogs bind, one of which unexpectedly can induce Siglec dimerization. In conjunction with in silico analysis, this set of structures informs us about the design of putative ligands with enhanced binding affinities and specificities to different Siglecs, and provides data with which to test the effectiveness of different computational drug design protocols.
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