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PMID: 17000723 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Potential source of Francisella tularensis live vaccine strain attenuation determined by genome comparison.

Infection and immunity ·Vol. 74 ·No. 12 ·2006-12-00 ·Pages 6895-906

Rohmer L, Brittnacher M, Svensson K, Buckley D, Haugen E, Zhou Y, Chang J, Levy R, Hayden H, Forsman M, Olson M, Johansson A, Kaul R, Miller SI

Abstract

Francisella tularensis is a bacterial pathogen that causes the zoonotic disease tularemia and is important to biodefense. Currently, the only vaccine known to confer protection against tularemia is a specific live vaccine strain (designated LVS) derived from a virulent isolate of Francisella tularensis subsp. holarctica. The origin and source of attenuation of this strain are not known. To assist with the design of a defined live vaccine strain, we sought to determine the genetic basis of the attenuation of LVS. This analysis relied primarily on the comparison between the genome of LVS and Francisella tularensis holarctica strain FSC200, which differ by only 0.08% of their nucleotide sequences. Under the assumption that the attenuation was due to a loss of function(s), only coding regions were examined in this comparison. To complement this analysis, the coding regions of two slightly more distantly related Francisella tularensis strains were also compared against the LVS coding regions. Thirty-five genes show unique sequence variations predicted to alter the protein sequence in LVS compared to the other Francisella tularensis strains. Due to these polymorphisms, the functions of 15 of these genes are very likely lost or impaired. Seven of these genes were demonstrated to be under stronger selective constraints, suggesting that they are the most probable to be the source of LVS attenuation and useful for a newly defined vaccine.

MeSH Terms
Bacterial Vaccines/genetics Base Sequence Conserved Sequence Evolution, Molecular Francisella tularensis/genetics,immunology Genes, Bacterial Genome, Bacterial/genetics Molecular Sequence Data Polymorphism, Genetic Tularemia/prevention & control Vaccines, Attenuated/genetics
Chemicals
Bacterial Vaccines Vaccines, Attenuated
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Rohmer Laurence
Department of Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA.
Brittnacher Mitchell
Svensson Kerstin
Buckley Danielle
Haugen Eric
Zhou Yang
Chang Jean
Levy Ruth
Hayden Hillary
Forsman Mats
Olson Maynard
Johansson Anders
Kaul Rajinder
Miller Samuel I
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.01006-06
Published
2006-12-00
Epub
2006-00-25
Pages
6895-906
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC1698093
Subset
IM
Grants
NIAID NIH HHS · R21 AI061106 · United States
NIAID NIH HHS · U54 AI057141 · United States
NIAID NIH HHS · 1R21 AI 061106-01 · United States
NIAID NIH HHS · U54 AI 057141 · United States
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External Links
PubMed source DOI: 10.1128/IAI.01006-06 PMC Full Text View journal details
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