000175994 001__ 175994
000175994 005__ 20181203022653.0
000175994 0247_ $$2doi$$a10.1016/j.chembiol.2011.12.016
000175994 02470 $$2ISI$$a000300917300009
000175994 037__ $$aARTICLE
000175994 245__ $$aCholesterol Catabolism by Mycobacterium tuberculosis Requires Transcriptional and Metabolic Adaptations
000175994 269__ $$a2012
000175994 260__ $$c2012
000175994 336__ $$aJournal Articles
000175994 520__ $$aTo understand the adaptation of Mycobacterium tuberculosis to the intracellular environment, we used comprehensive metabolite profiling to identify the biochemical pathways utilized during growth on cholesterol, a critical carbon source during chronic infection. Metabolic alterations observed during cholesterol catabolism centered on propionyl-CoA and pyruvate pools. Consequently, growth on this substrate required the transcriptional induction of the propionyl-CoA-assimilating methylcitrate cycle (MCC) enzymes, via the Rv1129c regulatory protein. We show that both Rv1129c and the MCC enzymes are required for intracellular growth in macrophages and that the growth defect of MCC mutants is largely attributable to the degradation of host-derived cholesterol. Together, these observations define a coordinated transcriptional and metabolic adaptation that is required for scavenging carbon during intracellular growth.
000175994 6531_ $$aCorynebacterium-Glutamicum
000175994 6531_ $$aMethylcitrate Cycle
000175994 6531_ $$aAcetate Metabolism
000175994 6531_ $$aIsocitrate Lyase-1
000175994 6531_ $$aPropionyl-Coa
000175994 6531_ $$aVirulence
000175994 6531_ $$aMacrophages
000175994 6531_ $$aGrowth
000175994 6531_ $$aGenes
000175994 6531_ $$aIdentification
000175994 700__ $$aGriffin, Jennifer E.$$uUniv Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA 01655 USA
000175994 700__ $$aPandey, Amit K.$$uUniv Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA 01655 USA
000175994 700__ $$aGilmore, Sarah A.
000175994 700__ $$aMizrahi, Valerie$$uUniv Cape Town, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa
000175994 700__ $$0243894$$aMckinney, John D.$$g177246$$uSwiss Fed Inst Technol Lausanne EPFL, Global Hlth Inst, Lausanne, Switzerland
000175994 700__ $$aBertozzi, Carolyn R.$$uHoward Hughes Med Inst, Chevy Chase, MD 20815 USA
000175994 700__ $$aSassetti, Christopher M.$$uUniv Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA 01655 USA
000175994 773__ $$j19$$q218-227$$tChemistry & Biology
000175994 909C0 $$0252303$$pUPKIN$$xU11741
000175994 909CO $$ooai:infoscience.tind.io:175994$$pSV$$particle
000175994 917Z8 $$x164606
000175994 937__ $$aEPFL-ARTICLE-175994
000175994 973__ $$aEPFL$$rREVIEWED$$sPUBLISHED
000175994 980__ $$aARTICLE