Open AccessChemical disarming of isoniazid resistance in Mycobacterium tuberculosis
Author(s) -
Kelly Flentie,
Gregory A. Harrison,
Hasan Tükenmez,
Jonathan Livny,
James A. D. Good,
Souvik Sarkar,
Dennis Zhu,
Rachel L. Kinsella,
Leslie A. Weiss,
Samantha D. Solomon,
Miranda E. Schene,
Mette Rud Hansen,
Andrew G. Cairns,
Martina Kulén,
Torbjörn Wixe,
Anders E. G. Lindgren,
Erik Chorell,
Christoffer Bengtsson,
K. Syam Krishnan,
Scott J. Hultgren,
Christer Larsson,
Fredrik Almqvist,
Christina L. Stallings
Publication year - 2019
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1818009116
Subject(s) - isoniazid , mycobacterium tuberculosis , tuberculosis , drug resistance , antibiotics , microbiology and biotechnology , drug tolerance , biology , mutant , prodrug , virology , gene , medicine , genetics , pharmacology , pathology
Significance Mycobacterium tuberculosis (Mtb ) causes the disease tuberculosis (TB), which kills more people than any other infection. The emergence of drug-resistantMtb strains has exacerbated this already alarming epidemic. We have identified a small molecule, C10, that potentiates the activity of the frontline antibiotic isoniazid (INH) and prevents the selection for INH-resistant mutants. We find that C10 can even reverse INH resistance inMtb . Therefore, our study reveals vulnerabilities that can be exploited to reverse INH resistance inMtb .
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