Genome diversity among regional populations of Francisella tularensis subspecies tularensis and Francisella tularensis subspecies holarctica isolated from the US

Abstract

Francisella tularensis is a highly infectious facultative intracellular pathogen that is considered a potential agent of bioterrorism. Four different F. tularensis subspecies have been identified and they appear to display different ecological and virulence characteristics as well as differences in geographical distribution. One simple explanation for the variation in ecological and virulence characteristics is that they are conferred by differences in genome content. To characterize genome content among stains isolated from United States, we have used a DNA microarray designed from a shotgun library of a reference strain. Polymorphisms distributed among polyphyletic sets of strains was the most common pattern of genome alteration observed, indicating that strain-specific genome variability is significant. Nonetheless, 13 different contiguous segments of the genome were found to be missing exclusively in each of the subsp. holarctica strains tested. All 13 are associated with repeat sequences or transposases that could promote insertion/deletion events. Comparison of the live vaccine strain to other holarctica strains also identified three regions that are absent exclusively in the live vaccine strain derived from holarctica.

A Mutant ofFrancisella tularensisStrain SCHU S4 Lacking the Ability To Express a 58-Kilodalton Protein Is Attenuated for Virulence and Is an Effective Live Vaccine

“…Although recent comparative genomic analyses have begun to demonstrate genetic differences among the subspecies, these alone have been insufficient to explain their relative virulence (2,14,21,28). It was recently shown that sublethal infection of mice with F. tularensis subsp.…”

Paired-End Sequence Mapping Detects Extensive Genomic Rearrangement and Translocation during Divergence of Francisella tularensis subsp. tularensis and Francisella tularensis subsp. holarctica Populations

“…Cultures for this study were propagated on chocolate agar at 37°C in 5% CO 2 . Glycerol fermentation was tested in a limited number of isolates, either as described previously (26) or by using Biolog (Biolog, Inc., Hayward, CA) according to the manufacturer's instructions. A summary of spatial, temporal, host, and other pertinent demographic information, as well as prior subspecies determinations of all strains and/or DNA used in this study, is listed in Table S1 in the supplemental material.…”

“…tularensis and has apparently been lost from the F. tularensis subsp. holarctica genome (4,26). Comparative genome-sequencing efforts are also under way and promise to provide detailed information with regard to specific strains.…”

Evolution of Subspecies of Francisella tularensis

“…c Region of difference independently identified by Samrakandi et al (21). RD18 and RD19 correspond to L3 and L2, respectively.…”