Regulation of Mycobacterium tuberculosis cell envelope composition and virulence by intramembrane proteolysis Journal Article
| Authors: | Makinoshima, H.; Glickman, M. S. |
| Article Title: | Regulation of Mycobacterium tuberculosis cell envelope composition and virulence by intramembrane proteolysis |
| Abstract: | Mycobacterium tuberculosis infection is a continuing global health crisis that kills 2 million people each year. Although the structurally diverse lipids of the M. tuberculosis cell envelope each have non-redundant roles in virulence or persistence, 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, membrane-bound transcription factors that control lipid biosynthesis. S2P is the founding member of a widely distributed family of membrane metalloproteases that cleave substrate proteins within transmembrane segments. 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. |
| Keywords: | controlled study; nonhuman; mouse; animal; cytology; metabolism; animals; mice; animal tissue; cell division; classification; protein degradation; molecular dynamics; animal experiment; animal model; in vivo study; physiology; virology; animalia; health care; growth, development and aging; mycolic acid; chemistry; mycobacterium tuberculosis; mycolic acids; protein processing; protein processing, post-translational; eukaryota; oligonucleotide array sequence analysis; cell membrane; dna microarray; proteinase; pathogenicity; mycobacterium; peptide hydrolases; tuberculosis; peptide hydrolase; cells; intramembrane proteolysis; biodiversity; prokaryote; prokaryota; virulence; bacterial membrane; biological membranes; growth kinetics; cell regulation; composition; tuberculosis infection; cellular organisms |
| Journal Title: | Nature |
| Volume: | 436 |
| Issue: | 7049 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2005-07-21 |
| Start Page: | 406 |
| End Page: | 409 |
| Language: | English |
| DOI: | 10.1038/nature03713 |
| PUBMED: | 16034419 |
| PROVIDER: | scopus |
| PMCID: | PMC1502149 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 43" - "Export Date: 24 October 2012" - "CODEN: NATUA" - "Source: Scopus" |
