Comparative Genomic Characterization of Francisella tularensis Strains Belonging to Low and High Virulence Subspecies

PLoS Pathogens

Paul Keim¹  Anders Sjöstedt²  Eli B. Nix³  Francis E. Nano³  Scott W. Bearden⁴  Richard Titball⁵  Sarah Young⁶  Reinhard Engels⁶  Matthew Pearson⁶  Mia D. Champion⁶  James Galagan⁶  Jared White⁶  Mark Borowsky⁶  Michael Koehrsen⁶  Lucia Alvarado⁶  Lisa Larson⁶  Mats Forsman⁶  Clint Howarth⁶  Qiandong Zeng⁶  Chinnappa D. Kodira⁷  Bruce Birren⁸  Stephen L. Michell⁸ 

[1] Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, United States of America;Centers for Disease Control and Prevention, Division of Vector-Borne Infectious Diseases, Fort Collins, Colorado, United States of America;Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada;Department of CBRN Defense and Security, Swedish Defense Research Agency, Umeå, Sweden;Department of Clinical Bacteriology, Clinical Microbiology, Umeå University, Umeå, Sweden;Microbial Analysis Group, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America;Pathogen Genomics Division, Translational Genomics Research Institute, Phoenix, Arizona, United States of America;University of Exeter, School of Biosciences, Exeter, United Kingdom

关键词: Francisella tularensis;    Francisella;    Comparative genomics;    DNA-binding proteins;    Secretion systems;    Gene disruption;    Sequence alignment;    Pseudogenes;   

DOI  :  10.1371/journal.ppat.1000459

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY