The goal of this project is to determine the DNA sequence of Francisella tularensis subspecies holarctica, the causative agent of tularemia. F. tularensis has been classified as a Category A Select Agent posing a serious military and civilian bioterrorism threat. Two strains of F. tularensis are currently being sequenced: a highly virulent type A strain and a type B (holarctica) strain used as a live vaccine. This project will determine the sequence of the genome of the parent of the vaccine strain. This strain is expected to retain intact virulence factors that have been altered in the vaccine strain, leading to its attenuation. Thus comparison of this sequence with that of the live vaccine strain as well as the type A strain will identify candidate genes for virulence factors. Moreover, sera from vaccinated individuals should be useful in identifying antigens in future studies, using the genomic sequence of the type B strain. Early results from genomic studies suggest that F. tularensis contains a high proportion of unique genes compared to other bacterial genomes. Therefore, knowledge of the complete genome sequences of F. tularensis strains is needed for the understanding of the virulence mechanisms. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI061106-01
Application #
6812541
Study Section
Special Emphasis Panel (ZRG1-IDM-A (90))
Program Officer
Schaefer, Michael R
Project Start
2004-07-15
Project End
2006-06-30
Budget Start
2004-07-15
Budget End
2006-06-30
Support Year
1
Fiscal Year
2004
Total Cost
$150,500
Indirect Cost
Name
Baylor College of Medicine
Department
Genetics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Petrosino, Joseph F; Xiang, Qin; Karpathy, Sandor E et al. (2006) Chromosome rearrangement and diversification of Francisella tularensis revealed by the type B (OSU18) genome sequence. J Bacteriol 188:6977-85
Rohmer, Laurence; Brittnacher, Mitchell; Svensson, Kerstin et al. (2006) Potential source of Francisella tularensis live vaccine strain attenuation determined by genome comparison. Infect Immun 74:6895-906