This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Su, J.
Right arrow Articles by Zhang, J.-R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Su, J.
Right arrow Articles by Zhang, J.-R.

 Previous Article  |  Next Article 

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.



This article has been cited by other articles:

  • Buchan, B. W., McCaffrey, R. L., Lindemann, S. R., Allen, L.-A. H., Jones, B. D. (2009). Identification of migR, a Regulatory Element of the Francisella tularensis Live Vaccine Strain iglABCD Virulence Operon Required for Normal Replication and Trafficking in Macrophages. Infect. Immun. 77: 2517-2529 [Abstract] [Full Text]  
  • LoVullo, E. D., Molins-Schneekloth, C. R., Schweizer, H. P., Pavelka, M. S. Jr (2009). Single-copy chromosomal integration systems for Francisella tularensis. Microbiology 155: 1152-1163 [Abstract] [Full Text]  
  • Kraemer, P. S., Mitchell, A., Pelletier, M. R., Gallagher, L. A., Wasnick, M., Rohmer, L., Brittnacher, M. J., Manoil, C., Skerett, S. J., Salama, N. R. (2009). Genome-Wide Screen in Francisella novicida for Genes Required for Pulmonary and Systemic Infection in Mice. Infect. Immun. 77: 232-244 [Abstract] [Full Text]  
  • Qin, A., Scott, D. W., Thompson, J. A., Mann, B. J. (2009). Identification of an Essential Francisella tularensis subsp. tularensis Virulence Factor. Infect. Immun. 77: 152-161 [Abstract] [Full Text]  
  • Clay, C. D., Soni, S., Gunn, J. S., Schlesinger, L. S. (2008). Evasion of Complement-Mediated Lysis and Complement C3 Deposition Are Regulated by Francisella tularensis Lipopolysaccharide O Antigen. J. Immunol. 181: 5568-5578 [Abstract] [Full Text]  
  • Hazlett, K. R. O., Caldon, S. D., McArthur, D. G., Cirillo, K. A., Kirimanjeswara, G. S., Magguilli, M. L., Malik, M., Shah, A., Broderick, S., Golovliov, I., Metzger, D. W., Rajan, K., Sellati, T. J., Loegering, D. J. (2008). Adaptation of Francisella tularensis to the Mammalian Environment Is Governed by Cues Which Can Be Mimicked In Vitro. Infect. Immun. 76: 4479-4488 [Abstract] [Full Text]  
  • Oyston, P. C. F. (2008). Francisella tularensis: unravelling the secrets of an intracellular pathogen. J Med Microbiol 57: 921-930 [Abstract] [Full Text]  
  • Zogaj, X., Chakraborty, S., Liu, J., Thanassi, D. G., Klose, K. E. (2008). Characterization of the Francisella tularensis subsp. novicida type IV pilus. Microbiology 154: 2139-2150 [Abstract] [Full Text]  
  • Ben Nasr, A., Klimpel, G. R. (2008). Subversion of complement activation at the bacterial surface promotes serum resistance and opsonophagocytosis of Francisella tularensis. J. Leukoc. Biol. 84: 77-85 [Abstract] [Full Text]  
  • Qin, A., Scott, D. W., Mann, B. J. (2008). Francisella tularensis subsp. tularensis Schu S4 Disulfide Bond Formation Protein B, but Not an RND-Type Efflux Pump, Is Required for Virulence. Infect. Immun. 76: 3086-3092 [Abstract] [Full Text]  
  • Buchan, B. W., McLendon, M. K., Jones, B. D. (2008). Identification of Differentially Regulated Francisella tularensis Genes by Use of a Newly Developed Tn5-Based Transposon Delivery System. Appl. Environ. Microbiol. 74: 2637-2645 [Abstract] [Full Text]  
  • Horzempa, J., Tarwacki, D. M., Carlson, P. E. Jr., Robinson, C. M., Nau, G. J. (2008). Characterization and Application of a Glucose-Repressible Promoter in Francisella tularensis. Appl. Environ. Microbiol. 74: 2161-2170 [Abstract] [Full Text]  
  • Maier, T. M., Casey, M. S., Becker, R. H., Dorsey, C. W., Glass, E. M., Maltsev, N., Zahrt, T. C., Frank, D. W. (2007). Identification of Francisella tularensis Himar1-Based Transposon Mutants Defective for Replication in Macrophages. Infect. Immun. 75: 5376-5389 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»