000151185 001__ 151185
000151185 005__ 20181203021956.0
000151185 022__ $$a1095-9203
000151185 02470 $$2PMID$$a19299584
000151185 02470 $$a000265832400051$$2ISI
000151185 0247_ $$2doi$$a10.1126/science.1171583
000151185 037__ $$aARTICLE
000151185 245__ $$aBenzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis
000151185 269__ $$a2009
000151185 260__ $$c2009
000151185 336__ $$aJournal Articles
000151185 520__ $$aNew drugs are required to counter the tuberculosis (TB) pandemic. Here, we describe the synthesis and characterization of 1,3-benzothiazin-4-ones (BTZs), a new class of antimycobacterial agents that kill Mycobacterium tuberculosis in vitro, ex vivo, and in mouse models of TB. Using genetics and biochemistry, we identified the enzyme decaprenylphosphoryl-beta-d-ribose 2'-epimerase as a major BTZ target. Inhibition of this enzymatic activity abolishes the formation of decaprenylphosphoryl arabinose, a key precursor that is required for the synthesis of the cell-wall arabinans, thus provoking cell lysis and bacterial death. The most advanced compound, BTZ043, is a candidate for inclusion in combination therapies for both drug-sensitive and extensively drug-resistant TB.
000151185 6531_ $$aCell-Wall
000151185 6531_ $$aIdentification
000151185 700__ $$aMakarov, Vadim
000151185 700__ $$0244382$$g196605$$aManina, Giulia
000151185 700__ $$aMikusova, Katarina
000151185 700__ $$aMöllmann, Ute
000151185 700__ $$aRyabova, Olga
000151185 700__ $$aSaint-Joanis, Brigitte
000151185 700__ $$0244375$$g178252$$aDhar, Neeraj
000151185 700__ $$aPasca, Maria Rosalia
000151185 700__ $$aBuroni, Silvia
000151185 700__ $$aLucarelli, Anna Paola
000151185 700__ $$aMilano, Anna
000151185 700__ $$aDe Rossi, Edda
000151185 700__ $$aBelanova, Martina
000151185 700__ $$aBobovska, Adela
000151185 700__ $$aDianiskova, Petronela
000151185 700__ $$aKordulakova, Jana
000151185 700__ $$0244366$$g179660$$aSala, Claudia
000151185 700__ $$aFullam, Elizabeth
000151185 700__ $$aSchneider, Patricia
000151185 700__ $$0243894$$g177246$$aMcKinney, John D.
000151185 700__ $$aBrodin, Priscille
000151185 700__ $$aChristophe, Thierry
000151185 700__ $$aWaddell, Simon
000151185 700__ $$aButcher, Philip
000151185 700__ $$aAlbrethsen, Jakob
000151185 700__ $$aRosenkrands, Ida
000151185 700__ $$aBrosch, Roland
000151185 700__ $$aNandi, Vrinda
000151185 700__ $$aBharath, Sowmya
000151185 700__ $$aGaonkar, Sheshagiri
000151185 700__ $$aShandil, Radha K.
000151185 700__ $$aBalasubramanian, Venkataraman
000151185 700__ $$aBalganesh, Tanjore
000151185 700__ $$aTyagi, Sandeep
000151185 700__ $$aGrosset, Jacques
000151185 700__ $$aRiccardi, Giovanna
000151185 700__ $$aCole, Stewart T.$$g177247$$0243892
000151185 773__ $$j324$$tScience (New York, N.Y.)$$k5928$$q801-4
000151185 909C0 $$xU11742$$0252302$$pUPCOL
000151185 909C0 $$xU11741$$0252303$$pUPKIN
000151185 909CO $$pSV$$particle$$ooai:infoscience.tind.io:151185
000151185 917Z8 $$x128933
000151185 937__ $$aEPFL-ARTICLE-151185
000151185 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000151185 980__ $$aARTICLE