We report the emergence of an atpE mutation in a clinical Mycobacterium tuberculosis strain. Genotypic and phenotypic bedaquiline susceptibility testing displayed variable results over time and ultimately were not predictive of treatment outcome. This observation highlights the limits of current genotypic and phenotypic methods for detection of bedaquiline resistance.
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http://dx.doi.org/10.3201/eid2805.212517 | DOI Listing |
J Biomol Struct Dyn
December 2024
Amity Institute of Biotechnology, Amity University, Kolkata, India.
The first FDA approved, MDR-TB inhibitory drug bedaquiline (BDQ), entraps the c-ring of the proton-translocating F region of enzyme ATP synthase of , thus obstructing successive ATP production. Present-day BDQ-resistance has been associated with cardiotoxicity and mutation(s) in the atpE gene encoding the c subunit of ATP synthase (ATPc) generating five distinct ATPc mutants: Ala63→Pro, Ile66→Met, Asp28→Gly, Asp28→Val and Glu61→Asp. We created three discrete libraries, first by repurposing bedaquiline via scaffold hopping approach, second one having natural plant compounds and the third being experimentally derived analogues of BDQ to identify one drug candidate that can inhibit ATPc activity more efficiently with less toxic properties.
View Article and Find Full Text PDFBMC Genomics
November 2024
Yunnan Key Laboratory of Konjac Biology, College of Agronomy, Yunnan Urban Agricultural Engineering and Technological Research Center, Kunming University, Kunming, China.
J Antimicrob Chemother
January 2025
National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China.
Objectives: The co-resistance between bedaquiline and clofazimine raises significant concerns, as they are commonly co-administered as core drugs in drug-resistant TB regimens. The present study aimed to monitor drug resistance-associated gene mutations and the phenotypic change in Mycobacterium tuberculosis (Mtb) under a stepwise drug resistance induction in vitro using bedaquiline, clofazimine or combined drugs.
Methods: Drug-resistant Mtb strains were gradually induced in vitro on a drug-containing solid medium with a 2-fold increasing concentration of bedaquiline, clofazimine and their combination.
J Clin Lab Anal
August 2024
Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Background: The treatment of multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) is a formidable challenge. Treatment of MDR- and XDR-TB using bedaquiline (BDQ) and delamanid (DLM), two newly introduced medications, is steadily increasing. This narrative review aimed to present a concise overview of the existing information regarding BDQ and DLM, and elucidate their antimicrobial characteristics, resistance mechanisms, synergism with other drugs, and side effects.
View Article and Find Full Text PDFPLoS One
September 2024
Gansu Agricultural University, Lanzhou, Gansu, China.
Tuberculosis has posed a serious threat to human health. It is imperative to investigate the geographic prevalence of tuberculosis and medication resistance, as this information is essential for informing strategies for its prevention and treatment. Drug resistance was identified using a proportion method.
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