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Science 26 May 2000:
Vol. 288. no. 5470, pp. 1436 - 1439
DOI: 10.1126/science.288.5470.1436
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Reports

Granuloma-Specific Expression of Mycobacterium Virulence Proteins from the Glycine-Rich PE-PGRS Family

Lalita Ramakrishnan, 1* Nancy A. Federspiel, 2 Stanley Falkow 1

Pathogenic mycobacteria, including the agent of tuberculosis, Mycobacterium tuberculosis, must replicate in macrophages for long-term persistence within their niche during chronic infection: organized collections of macrophages and lymphocytes called granulomas. We identified several genes preferentially expressed when Mycobacterium marinum, the cause of fish and amphibian tuberculosis, resides in host granulomas and/or macrophages. Two were homologs of M. tuberculosis PE/PE-PGRS genes, a family encoding numerous repetitive glycine-rich proteins of unknown function. Mutation of two PE-PGRS genes produced M. marinum strains incapable of replication in macrophages and with decreased persistence in granulomas. Our results establish a direct role in virulence for some PE-PGRS proteins.

1 Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
2 Department of Biochemistry, Stanford Center for DNA Sequence and Technology, Palo Alto, CA 94304, USA.
*   To whom correspondence should be addressed. E-mail: lalitar{at}cmgm.stanford.edu

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