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Journal of Bacteriology, October 2004, p. 6430-6436, Vol. 186, No. 19
0021-9193/04/$08.00+0     DOI: 10.1128/JB.186.19.6430-6436.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

A Francisella tularensis Pathogenicity Island Required for Intramacrophage Growth

Francis E. Nano,1* Na Zhang,1 Siobhán C. Cowley,2 Karl E. Klose,3 Karen K. M. Cheung,1 Michael J. Roberts,1 Jagjit S. Ludu,1 Gregg W. Letendre,1 Anda I. Meierovics,2 Gwen Stephens,4 and Karen L. Elkins2

Department of Biochemistry and Microbiology, University of Victoria, Victoria,1 British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada,4 Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland,2 Department of Microbiology and Immunology, University of Texas Health Sciences Center, San Antonio, Texas3

Received 19 May 2004/ Accepted 30 June 2004

Francisella tularensis is a gram-negative, facultative intracellular pathogen that causes the highly infectious zoonotic disease tularemia. We have discovered a ca. 30-kb pathogenicity island of F. tularensis (FPI) that includes four large open reading frames (ORFs) of 2.5 to 3.9 kb and 13 ORFs of 1.5 kb or smaller. Previously, two small genes located near the center of the FPI were shown to be needed for intramacrophage growth. In this work we show that two of the large ORFs, located toward the ends of the FPI, are needed for virulence. Although most genes in the FPI encode proteins with amino acid sequences that are highly conserved between high- and low-virulence strains, one of the FPI genes is present in highly virulent type A F. tularensis, absent in moderately virulent type B F. tularensis, and altered in F. tularensis subsp. novicida, which is highly virulent for mice but avirulent for humans. The G+C content of a 17.7-kb stretch of the FPI is 26.6%, which is 6.6% below the average G+C content of the F. tularensis genome. This extremely low G+C content suggests that the DNA was imported from a microbe with a very low G+C-containing chromosome.

* Corresponding author. Mailing address: Department of Biochemistry and Microbiology, P.O. Box 3055 STN CSC, University of Victoria, Victoria, B.C. V8W 3P6, Canada. Phone: (250) 721-7074. Fax: (250) 721-8855. E-mail: fnano{at}uvic.ca.

Journal of Bacteriology, October 2004, p. 6430-6436, Vol. 186, No. 19
0021-9193/04/$08.00+0     DOI: 10.1128/JB.186.19.6430-6436.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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