Regulation of Mycobacterium tuberculosis cell envelope composition and virulence by intramembrane proteolysis

Article

关键词: STRESS-RESPONSE;    BOVIS BCG;    BIOSYNTHESIS;    CLEAVAGE;    MICE;    IDENTIFICATION;    SURVIVAL;    PATHWAY;    RSEA;   

DOI  :  10.1038/nature03713

来源: SCIE

【 摘 要 】

Mycobacterium tuberculosis infection is a continuing global health crisis that kills 2 million people each year(1). Although the structurally diverse lipids of the M. tuberculosis cell envelope each have non-redundant roles in virulence or persistence(2-7), the molecular mechanisms regulating cell envelope composition in M. tuberculosis are undefined. In higher eukaryotes, membrane composition is controlled by site two protease (S2P)-mediated cleavage of sterol regulatory element binding proteins(8,9), membrane-bound transcription factors that control lipid biosynthesis. S2P is the founding member of a widely distributed family of membrane metalloproteases(10,11) that cleave substrate proteins within transmembrane segments(12). Here we show that a previously uncharacterized M. tuberculosis S2P homologue (Rv2869c) regulates M. tuberculosis cell envelope composition, growth in vivo and persistence in vivo. These results establish that regulated intramembrane proteolysis is a conserved mechanism controlling membrane composition in prokaryotes and show that this proteolysis is a proximal regulator of cell envelope virulence determinants in M. tuberculosis.

【 授权许可】

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