000186546 001__ 186546
000186546 005__ 20180913061911.0
000186546 0247_ $$2doi$$a10.1098/rsob.120175
000186546 022__ $$a2046-2441
000186546 02470 $$2ISI$$a000316942200005
000186546 037__ $$aARTICLE
000186546 245__ $$aA vitamin B-12 transporter in Mycobacterium tuberculosis
000186546 260__ $$aLondon$$bRoyal Society, The$$c2013
000186546 269__ $$a2013
000186546 300__ $$a10
000186546 336__ $$aJournal Articles
000186546 520__ $$aVitamin B-12-depende enzymes function in core biochemical pathways in Mycobacterium tuberculosis, an obligate pathogen whose metabolism in vivo is poorly understood. Although M. tuberculosis can access vitamin B-12 in vitro, it is uncertain whether the organism is able to scavenge B-12 during host infection. This question is crucial to predictions of metabolic function, but its resolution is complicated by the absence in the M. tuberculosis genome of a direct homologue of BtuFCD, the only bacterial B-12 transport system described to date. We applied genome-wide transposon mutagenesis to identify M. tuberculosis mutants defective in their ability to use exogenous B-12. A small proportion of these mapped to Rv1314c, identifying the putative PduO-type ATP : co(I) rrinoid adenosyltransferase as essential for B-12 assimilation. Most notably, however, insertions in Rv1819c dominated the mutant pool, revealing an unexpected function in B-12 acquisition for an ATP-binding cassette (ABC)-type protein previously investigated as the mycobacterial BacA homologue. Moreover, targeted deletion of Rv1819c eliminated the ability of M. tuberculosis to transport B-12 and related corrinoids in vitro. Our results establish an alternative to the canonical BtuCD-type system for B-12 uptake in M. tuberculosis, and elucidate a role in B-12 metabolism for an ABC protein implicated in chronic mycobacterial infection.
000186546 6531_ $$atuberculosis
000186546 6531_ $$avitamin B-12
000186546 6531_ $$acorrinoids
000186546 6531_ $$aBtuFCD
000186546 6531_ $$aBacA
000186546 700__ $$aGopinath, Krishnamoorthy$$uUniv Cape Town, MRC NHLS UCT Mol Mycobacteriol Res Unit, Fac Hlth Sci, ZA-7925 Cape Town, South Africa
000186546 700__ $$aVenclovas, Ceslovas$$uInst Biotechnol, Lab Bioinformat, Vilnius, Lithuania
000186546 700__ $$aIoerger, Thomas R.$$uTexas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA
000186546 700__ $$aSacchettini, James C.$$uTexas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA
000186546 700__ $$0243894$$aMcKinney, John D.$$g177246
000186546 700__ $$aMizrahi, Valerie$$uUniv Cape Town, MRC NHLS UCT Mol Mycobacteriol Res Unit, Fac Hlth Sci, ZA-7925 Cape Town, South Africa
000186546 700__ $$aWarner, Digby F.$$uUniv Cape Town, MRC NHLS UCT Mol Mycobacteriol Res Unit, Fac Hlth Sci, ZA-7925 Cape Town, South Africa
000186546 773__ $$j3$$tOpen Biology
000186546 909C0 $$0252303$$pUPKIN$$xU11741
000186546 909CO $$ooai:infoscience.tind.io:186546$$pSV$$particle
000186546 917Z8 $$x164606
000186546 937__ $$aEPFL-ARTICLE-186546
000186546 973__ $$aEPFL$$rREVIEWED$$sPUBLISHED
000186546 980__ $$aARTICLE