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Infection and Immunity, June 2007, p. 3089-3101, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.01865-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Genome-Wide Identification of Francisella tularensis Virulence Determinants{triangledown}

Jingliang Su,1 Jun Yang,1 Daimin Zhao,1 Thomas H. Kawula,2 Jeffrey A. Banas,1,{dagger} and Jing-Ren Zhang1*

Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York 12208,1 Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 275992

Received 27 November 2006/ Returned for modification 24 December 2006/ Accepted 24 March 2007

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-{gamma}-glutamate capsule biosynthesis locus of Bacillus anthracis, the anthrax agent. Deletional mutation analysis confirmed that this locus is essential for F. tularensis virulence.

* Corresponding author. Mailing address: Center for Immunology and Microbial Disease, Albany Medical College, M/C 151, Room MS453, 47 New Scotland Avenue, Albany, NY 12208. Phone: (518) 262-6412. Fax: (518) 262-6161. E-mail: zhangj{at}mail.amc.edu

{triangledown} Published ahead of print on 9 April 2007.

Editor: A. Camilli

{dagger} Present address: University of Iowa College of Dentistry, Iowa City, IA 52242.

Infection and Immunity, June 2007, p. 3089-3101, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.01865-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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