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Genetic regulation of vesiculogenesis and immunomodulation in Mycobacterium tuberculosis.

ABSTRACT: Mycobacterium tuberculosis (Mtb) restrains immune responses well enough to escape eradication but elicits enough immunopathology to ensure its transmission. Here we provide evidence that this host-pathogen relationship is regulated in part by a cytosolic, membrane-associated protein with a unique structural fold, encoded by the Mtb gene rv0431. The protein acts by regulating the quantity of Mtb-derived membrane vesicles bearing Toll-like receptor 2 ligands, including the lipoproteins LpqH and SodC. We propose that rv0431 be named "vesiculogenesis and immune response regulator."

SUBMITTER: Rath P

PROVIDER: S-EPMC3856836 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Genetic regulation of vesiculogenesis and immunomodulation in Mycobacterium tuberculosis.

Rath Poonam P Huang Chengdong C Wang Tao T Wang Tianzhi T Li Huilin H Prados-Rosales Rafael R Elemento Olivier O Casadevall Arturo A Nathan Carl F CF

Proceedings of the National Academy of Sciences of the United States of America 20131118 49

Mycobacterium tuberculosis (Mtb) restrains immune responses well enough to escape eradication but elicits enough immunopathology to ensure its transmission. Here we provide evidence that this host-pathogen relationship is regulated in part by a cytosolic, membrane-associated protein with a unique structural fold, encoded by the Mtb gene rv0431. The protein acts by regulating the quantity of Mtb-derived membrane vesicles bearing Toll-like receptor 2 ligands, including the lipoproteins LpqH and So ...[more]

PMID: 24248369

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A Novel Gene Regulates Vesiculogenesis and Immunomodulation in Mycobacterium tuberculosis

Project description:After co-evolving with humans, its only major host, Mycobacterium tuberculosis (Mtb) restrains immune responses well enough to escape eradication, yet elicits enough immunopathology to ensure its transmission. Here, we provide evidence that this balance is regulated in part by a previously uncharacterized, cytosolic, membrane-associated protein with a novel structural fold, encoded by the Mtb gene rv0431. The protein acts by regulating the quantity and quality of Mtb-derived membrane vesicles bearing TLR2 ligands, including the lipoproteins LpqH and SodC. We propose that rv0431 be named virR (vesiculogenesis and immune response regulator). To our knowledge, VirR is the first bacterial protein identified to regulate vesiculogenesis. Transcriptome sequencing of mouse macrophages uninfected, infected with WT Mtb, or infected with rv0431 mutant Mtb.

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A Novel Gene Regulates Vesiculogenesis and Immunomodulation in Mycobacterium tuberculosis

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