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Title: Naturally-occurring polymorphisms in QcrB are responsible for resistance to Telacebec in Mycobacterium abscessus
Authors: Sorayah, Ria
Manimekalai, Malathy Sony Subramanian
Shin, Sung Jae
Koh, Won-Jung
Grüber, Gerhard
Pethe, Kevin
Keywords: Science::Medicine
Issue Date: 2019
Source: Sorayah, R., Manimekalai, M. S. S., Shin, S. J., Koh, W., Grüber, G. & Pethe, K. (2019). Naturally-occurring polymorphisms in QcrB are responsible for resistance to Telacebec in Mycobacterium abscessus. ACS Infectious Diseases, 5(12), 2055-2060.
Journal: ACS Infectious Diseases
Abstract: Mycobacterium abscessus (M. abscessus) is a rapidly growing nontuberculous mycobacteria that is quickly emerging as a global health concern. M. abscessus pulmonary infections are frequently intractable due to the high intrinsic resistance to most antibiotics. Therefore, there is an urgent need to discover effective pharmacological options for M. abscessus infections. In this study, the potency of the antituberculosis drug Telacebec (Q203) was evaluated against M. abscessus. Q203 is a clinical-stage drug candidate targeting the subunit QcrB of the cytochrome bc1:aa3 terminal oxidase. We demonstrated that the presence of four naturally-occurring polymorphisms in the M. abscessus QcrB is responsible for the high resistance of the bacterium to Q203. Genetics reversion of the four polymorphisms sensitized M. abscessus to Q203. While this study highlights the limitation of a direct drug repurposing approach of Q203 and related drugs for M. abscessus infections, it reveals that the M. abscessus cytochrome bc1:aa3 respiratory branch is sensitive to chemical inhibition.
ISSN: 2373-8227
DOI: 10.1021/acsinfecdis.9b00322
Rights: This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Infectious Diseases, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see
Fulltext Permission: open
Fulltext Availability: With Fulltext
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