par Hana L, Haver;Chua, Adeline;Pramila, Ghode;Lakshminarayana, Suresh SB;Singhal, Amit;Mathema, Barun;Wintjens, René ;Bifani, Pablo
Référence Antimicrobial agents and chemotherapy, 59, 9, page (5316-5323)
Publication Publié, 2015-09
Référence Antimicrobial agents and chemotherapy, 59, 9, page (5316-5323)
Publication Publié, 2015-09
Article révisé par les pairs
Résumé : | Alleviating the burden of tuberculosis (TB) requires an understanding of the genetic basis that determines the emergence of drug-resistant mutants. PA-824 (pretomanid) is a bicyclic nitroimidazole class compound presently undergoing the phase III STAND clinical trial, despite lacking identifiable genetic markers for drug-specific resistant Mycobacterium tuberculosis. In the present study, we aimed to characterize the genetic polymorphisms of spontaneously generated PA-824-resistant mutant strains by surveying drug metabolism genes for potential mutations. Of the 183 independently selected PA-824-resistant M. tuberculosis mutants, 83% harbored a single mutation in one of five nonessential genes associated with either PA-824 prodrug activation (ddn, 29%; fgd1, 7%) or the tangential F |