Naturally-Occurring Polymorphisms in QcrB Are Responsible for Resistance to Telacebec in Mycobacterium abscessus

Ria Sorayah, Malathy Sony Subramanian Manimekalai, Sung Jae Shin, Won Jung Koh, Gerhard Grüber, Kevin Pethe

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2055-2060
Number of pages6
JournalACS Infectious Diseases
Issue number12
Publication statusPublished - 2019 Dec 13

Bibliographical note

Funding Information:
This research is supported by the Lee Kong Chian School of Medicine, Nanyang Technological University Start-Up Grant (awarded to K.P.). R.S. is supported by a scholarship from NTU Institute for Health Technologies (HealthTech NTU), Interdisciplinary Graduate Programme, Nanyang Technological University.

Publisher Copyright:
© 2019 American Chemical Society.

All Science Journal Classification (ASJC) codes

  • Infectious Diseases


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