Abstract
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.
Publication types
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Comment
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Bacterial Proteins / chemistry
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Bacterial Proteins / genetics*
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Cells, Cultured
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Disease Models, Animal
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Gene Expression Profiling
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Gene Expression Regulation, Bacterial
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Genes, Bacterial
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Glycine / analysis
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Granuloma / microbiology*
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Granuloma / pathology
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Humans
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Macrophages / microbiology*
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Mutation
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Mycobacterium Infections, Nontuberculous / microbiology*
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Mycobacterium Infections, Nontuberculous / pathology
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Mycobacterium marinum / genetics*
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Mycobacterium marinum / growth & development
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Mycobacterium marinum / pathogenicity*
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Mycobacterium tuberculosis / genetics
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Mycobacterium tuberculosis / pathogenicity
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Promoter Regions, Genetic
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Rana pipiens
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Tuberculosis / microbiology
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Virulence
Substances
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Bacterial Proteins
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Glycine