000226876 001__ 226876
000226876 005__ 20181203024619.0
000226876 0247_ $$2doi$$a10.1038/srep43495
000226876 022__ $$a2045-2322
000226876 02470 $$2ISI$$a000394936400001
000226876 037__ $$aARTICLE
000226876 245__ $$aEssentiality of mmpL3 and impact of its silencing on Mycobacterium tuberculosis gene expression
000226876 260__ $$aLondon$$bNature Publishing Group$$c2017
000226876 269__ $$a2017
000226876 300__ $$a8
000226876 336__ $$aJournal Articles
000226876 520__ $$aMmpL3 is an inner membrane transporter of Mycobacterium tuberculosis responsible for the export of trehalose momomycolate, a precursor of the mycobacterial outer membrane component trehalose dimycolate (TDM), as well as mycolic acids bound to arabinogalactan. MmpL3 represents an emerging target for tuberculosis therapy. In this paper, we describe the construction and characterization of an mmpL3 knockdown strain of M. tuberculosis. Downregulation of mmpL3 led to a stop in bacterial division and rapid cell death, preceded by the accumulation of TDM precursors. MmpL3 was also shown to be essential for growth in monocyte-derived human macrophages. Using RNA-seq we also found that MmpL3 depletion caused up-regulation of 47 genes and down-regulation of 23 genes (at least 3-fold change and false discovery rate <= 1%). Several genes related to osmoprotection and metal homeostasis were induced, while several genes related to energy production and mycolic acids biosynthesis were repressed suggesting that inability to synthesize a correct outer membrane leads to changes in cellular permeability and a metabolic downshift.
000226876 700__ $$aDegiacomi, Giulia$$uUniv Padua, Dept Mol Med, Padua, Italy
000226876 700__ $$0246601$$aBenjak, Andrej$$g229809$$uEcole Polytech Fed Lausanne, Global Hlth Inst, Lausanne, Switzerland
000226876 700__ $$aMadacki, Jan$$uComenius Univ, Dept Biochem, Fac Nat Sci, Bratislava, Slovakia
000226876 700__ $$aBoldrin, Francesca$$uUniv Padua, Dept Mol Med, Padua, Italy
000226876 700__ $$aProvvedi, Roberta
000226876 700__ $$aPalu, Giorgio$$uUniv Padua, Dept Mol Med, Padua, Italy
000226876 700__ $$aKordulakova, Jana$$uComenius Univ, Dept Biochem, Fac Nat Sci, Bratislava, Slovakia
000226876 700__ $$0243892$$aCole, Stewart T.$$g177247$$uEcole Polytech Fed Lausanne, Global Hlth Inst, Lausanne, Switzerland
000226876 700__ $$aManganelli, Riccardo$$uUniv Padua, Dept Mol Med, Padua, Italy
000226876 773__ $$j7$$q43495$$tScientific Reports
000226876 909C0 $$0252302$$pUPCOL$$xU11742
000226876 909CO $$ooai:infoscience.tind.io:226876$$pSV$$particle
000226876 917Z8 $$x282550
000226876 937__ $$aEPFL-ARTICLE-226876
000226876 973__ $$aEPFL$$rREVIEWED$$sPUBLISHED
000226876 980__ $$aARTICLE