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The genetic composition and diversity of Francisella tularensis
Umeå University, Faculty of Medicine, Clinical Microbiology.
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Francisella tularensis is the causative agent of the debilitating, sometimes fatal zoonotic disease tularemia. To date, little information has been available on the genetic makeup of this pathogen, its evolution, and the genetic differences which characterize subspecific lineages. These are the main areas addressed in this thesis.

The work indicated a high degree of genetic conservation of F. tularensis, both on the sequence level as determined by sequencing and on the compositional level, determined by array-based comparative genomic hybridizations (aCGH). One striking finding was that subsp. mediasiatica was most similar to subsp. tularensis, despite their natural confinement to Central Asia and North America, respectively. All genetic Regions of Difference RD found by aCGH distinguishing lineages were had resulted from repeat-mediated excision of DNA. This was used to identify additional RDs. Such data along with a multiple locus sequence analysis suggested an evolutionary scenario for F. tularensis.

Based on genomic information, a novel typing scheme for F. tularensis was furthermore devised and evaluated. This method provided increased robustness compared to previously used methods for F. tularensis typing, while retaining a capacity for high resolution.

Finally, the genomic sequence of the highly virulent F. tularensis strain SCHU S4 was determined and analysed. Evidenced by numerous pseudogenes and disrupted metabolic pathways, the bacterium appears to be undergoing a genome reduction process whereby a large proportion of the genetic capacity gradually is lost. It is likely that F. tularensis has irreversibly has evolved into an obligate host-dependent bacterium, incapable of a free-living existence. Unexpectedly, the bacterium was found to be devoid of common virulence mechanisms such as classic toxins, or type III and IV secretion systems. Instead, the virulence of this bacterium is probably largely the result of specific and unusual mechanisms.

Place, publisher, year, edition, pages
Umeå: Klinisk mikrobiologi , 2007. , 51 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1094
Keyword [en]
Microbiology, tularemia, genotyping, evolution, microarray, genome sequencing, virulence, genome reduction
Keyword [sv]
Mikrobiologi
Keyword [la]
Francisella tularensis
Research subject
Clinical Bacteriology
Identifiers
URN: urn:nbn:se:umu:diva-1139ISBN: 971-91-7264-288-1-X OAI: oai:DiVA.org:umu-1139DiVA: diva2:140351
Public defence
2007-05-31, E04, 6E, NUS, Umeå, 09:00
Opponent
Supervisors
Available from: 2007-05-11 Created: 2007-05-11Bibliographically approved
List of papers
1. 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 subsp. tularensis.
Open this publication in new window or tab >>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 subsp. tularensis.
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2003 (English)In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 41, no 7, 2924-2931 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-2381 (URN)12843022 (PubMedID)
Available from: 2007-05-11 Created: 2007-05-11 Last updated: 2017-12-14Bibliographically approved
2. Evolution of subspecies of Francisella tularensis
Open this publication in new window or tab >>Evolution of subspecies of Francisella tularensis
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2005 (English)In: Journal of Bacteriology, ISSN 0021-9193, E-ISSN 1098-5530, Vol. 187, no 11, 3903-3908 p.Article in journal (Refereed) Published
Abstract [en]

Analysis of unidirectional genomic deletion events and single nucleotide variations suggested that the four subspecies of Francisella tularensis have evolved by vertical descent. The analysis indicated an evolutionary scenario where the highly virulent F. tularensis subsp. tularensis (type A) appeared before the less virulent F. tularensis subsp. holarctica (type B). Compared to their virulent progenitors, attenuated strains of F. tularensis exhibited specific unidirectional gene losses.

Keyword
Evolution; Molecular, Francisella tularensis/classification/*genetics/pathogenicity, Gene Deletion, Genome; Bacterial, Molecular Sequence Data, Oligonucleotide Array Sequence Analysis, Phylogeny, Virulence
Identifiers
urn:nbn:se:umu:diva-2382 (URN)10.1128/JB.187.11.3903-3908.2005 (DOI)15901721 (PubMedID)
Available from: 2007-05-11 Created: 2007-05-11 Last updated: 2017-12-14Bibliographically approved
3. Analysis of insertion-deletion markers with canonical properties for safe and rapid DNA-based typing of Francisella tularensis
Open this publication in new window or tab >>Analysis of insertion-deletion markers with canonical properties for safe and rapid DNA-based typing of Francisella tularensis
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(English)Article in journal (Refereed) Submitted
Identifiers
urn:nbn:se:umu:diva-2383 (URN)
Available from: 2007-05-11 Created: 2007-05-11 Last updated: 2016-03-01Bibliographically approved
4. The complete genome sequence of Francisella tularensis, the causative agent of tularemia.
Open this publication in new window or tab >>The complete genome sequence of Francisella tularensis, the causative agent of tularemia.
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2005 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 37, 153-159 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-2384 (URN)10.1038/ng1499 (DOI)15640799 (PubMedID)
Available from: 2007-05-11 Created: 2007-05-11 Last updated: 2017-12-14Bibliographically approved

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