Granuloma-specific expression of Mycobacterium virulence proteins from theglycine-rich PE-PGRS family

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