Granuloma-specific expression of Mycobacterium virulence proteins from the glycine-rich PE-PGRS family.
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.
Ramakrishnan
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L
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. lalitar@cmgm.stanford.edu
Federspiel
N A
NA
Falkow
S
S
D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D005998:Glycine / Q000032:analysis; D006099:Granuloma / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D009154:Mutation; D009165:Mycobacterium Infections, Nontuberculous / Q000382:microbiology* / Q000473:pathology; D019910:Mycobacterium marinum / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity*; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000472:pathogenicity; D011401:Promoter Regions, Genetic; D011894:Rana pipiens; D014376:Tuberculosis / Q000382:microbiology; D014774:Virulence
D001426:Bacterial Proteins; D005998:Glycine