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Genome-Wide Identification of Francisella tularensis Virulence Determinants
Journal article   Open access   Peer reviewed

Genome-Wide Identification of Francisella tularensis Virulence Determinants

Jingliang Su, Jun Yang, Daimin Zhao, Thomas H Kawula, Jeffrey A Banas and Jing-Ren Zhang
Infection and immunity, Vol.75(6), pp.3089-3101
06/2007
DOI: 10.1128/IAI.01865-06
PMCID: PMC1932872
PMID: 17420240
url
https://doi.org/10.1128/IAI.01865-06View
Published (Version of record) Open Access

Abstract

Francisella tularensis is a gram-negative pathogen that causes life-threatening infections in humans and has potential for use as a biological weapon. The genetic basis of the F. tularensis virulence is poorly understood. This study screened a total of 3,936 transposon mutants of the live vaccine strain for infection in a mouse model of respiratory tularemia by signature-tagged mutagenesis. We identified 341 mutants attenuated for infection in the lungs. The transposon disruptions were mapped to 95 different genes, virtually all of which are also present in the genomes of other F. tularensis strains, including human pathogenic F. tularensis strain Schu S4. A small subset of these attenuated mutants carried insertions in the genes encoding previously known virulence factors, but the majority of the identified genes have not been previously linked to F. tularensis virulence. Among these are genes encoding putative membrane proteins, proteins associated with stress responses, metabolic proteins, transporter proteins, and proteins with unknown functions. Several attenuated mutants contained disruptions in a putative capsule locus which partially resembles the poly-γ-glutamate capsule biosynthesis locus of Bacillus anthracis , the anthrax agent. Deletional mutation analysis confirmed that this locus is essential for F. tularensis virulence.
Molecular Pathogenesis

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