Open Access<p>Comparison of in vitro Susceptibility of Mycobacteria Against PA-824 to Identify Key Residues of Ddn, the Deazoflavin-Dependent Nitroreductase from <em>Mycobacterium tuberculosis</em></p>
Author(s) -
Fuzhen Zhang,
Shanshan Li,
Shu’an Wen,
Tingting Zhang,
Yuanyuan Shang,
Fengmin Huo,
Yi Xue,
Ling Li,
Yu Pang
Publication year - 2020
Publication title -
infection and drug resistance
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.033
H-Index - 39
ISSN - 1178-6973
DOI - 10.2147/idr.s240716
Subject(s) - mycobacterium smegmatis , nitroreductase , mycobacterium , mycobacterium tuberculosis , mycobacterium kansasii , microbiology and biotechnology , mycobacterium abscessus , nontuberculous mycobacteria , in vitro , chemistry , biology , biochemistry , tuberculosis , bacteria , enzyme , medicine , genetics , pathology
PA-824 (Pretomanid), a bicyclic nitroimidazole drug, exhibits significant bactericidal activity toward Mycobacterium tuberculosis (MTB) in vitro and in vivo, but not against Mycobacterium smegmatis . Through catalytic bioreduction, deazaflavin-dependent nitroreductase (Ddn) within MTB directly converts PA-824 to potent bactericidal products. This study aimed to identify key MTB Ddn residues involved in PA-824 conversion toward development of in vitro surrogate markers for detection of mycobacterial resistance to PA-824.