000266896 001__ 266896
000266896 005__ 20190625154533.0
000266896 022__ $$a0950-382X
000266896 022__ $$a1365-2958
000266896 02470 $$a000466177100011$$2isi
000266896 0247_ $$a10.1111/mmi.14220$$2doi
000266896 037__ $$aARTICLE
000266896 245__ $$aIncreased drug permeability of a stiffened mycobacterial outer membrane in cells lacking MFS transporter Rv1410 and lipoprotein LprG
000266896 260__ $$c2019$$aHoboken$$bWILEY
000266896 269__ $$a2019-05-01
000266896 336__ $$aJournal Articles
000266896 520__ $$aThe major facilitator superfamily transporter Rv1410 and the lipoprotein LprG (Rv1411) are encoded by a conserved two-gene operon and contribute to virulence in Mycobacterium tuberculosis. Rv1410 was originally postulated to function as a drug efflux pump, but recent studies suggested that Rv1410 and LprG work in concert to insert triacylglycerides and lipoarabinomannans into the outer membrane. Here, we conducted microscopic analyses of Mycobacterium smegmatis lacking the operon and observed a cell separation defect, while surface rigidity measured by atomic force microscopy was found to be increased. Whereas Rv1410 expressed in Lactococcus lactis did not confer drug resistance, deletion of the operon in Mycobacterium abscessus and M. smegmatis resulted in increased susceptibility toward vancomycin, novobiocin and rifampicin. A homology model of Rv1410 revealed a periplasmic loop as well as a highly conserved aspartate, which were found to be essential for the operon's function. Interestingly, influx of the fluorescent dyes BCECF-AM and calcein-AM in de-energized M. smegmatis cells was faster in the deletion mutant. Our results unambiguously show that elevated drug susceptibility in the deletion mutant is caused by increased drug influx through a defective mycobacterial cell envelope and not by drug efflux mediated by Rv1410.
000266896 650__ $$aBiochemistry & Molecular Biology
000266896 650__ $$aMicrobiology
000266896 650__ $$aBiochemistry & Molecular Biology
000266896 650__ $$aMicrobiology
000266896 6531_ $$ahigh-throughput cloning
000266896 6531_ $$amultidrug efflux pump
000266896 6531_ $$aescherichia-coli
000266896 6531_ $$aresistance
000266896 6531_ $$atuberculosis
000266896 6531_ $$aproteins
000266896 6531_ $$adivision
000266896 6531_ $$abiosynthesis
000266896 6531_ $$ainfections
000266896 6531_ $$aabscessus
000266896 700__ $$aHohl, Michael
000266896 700__ $$aRemm, Sille
000266896 700__ $$aEskandarian, Haig A.$$0247704$$g241028
000266896 700__ $$aDal Molin, Michael
000266896 700__ $$aArnold, Fabian M.
000266896 700__ $$aHuerlimann, Lea M.
000266896 700__ $$aKruegel, Andri
000266896 700__ $$aFantner, Georg E.$$0244716$$g199129
000266896 700__ $$aSander, Peter
000266896 700__ $$aSeeger, Markus A.
000266896 773__ $$k5$$j111$$q1263-1282$$tMolecular Microbiology
000266896 8560_ $$fsuzanne.balharry@epfl.ch
000266896 909C0 $$mgeorg.fantner@epfl.ch$$zMarselli, Béatrice$$xU12183$$yApproved$$0252332$$pLBNI
000266896 909C0 $$yApproved$$pUPKIN$$xU11741$$msuzanne.balharry@epfl.ch$$zBlumer, Eliane$$0252303
000266896 909CO $$particle$$ooai:infoscience.epfl.ch:266896$$pSTI$$pSV
000266896 961__ $$avalerie.charbonnier@epfl.ch
000266896 973__ $$aEPFL$$sPUBLISHED$$rREVIEWED
000266896 980__ $$aARTICLE
000266896 980__ $$aWoS
000266896 981__ $$aoverwrite