Low-level BTZ-043 resistance in <i>Mycobacterium tuberculosis</i> and cross-resistance to bedaquiline and clofazimine.

ABSTRACT:

Background

Multidrug- and extensively drug-resistant strains of Mycobacterium tuberculosis complex (MTBC) remain a significant global health challenge. This study investigates resistance mechanisms to BTZ-043, a novel decaprenylphosphoryl-β-D-ribose 2'-epimerase (DprE1) inhibitor, and its potential cross-resistance with bedaquiline (BDQ) and clofazimine (CFZ).

Methods

BTZ-043-resistant mutants were generated in M. tuberculosis H37Rv by serial exposure to escalating drug concentrations. Minimum inhibitory concentrations (MICs) for BTZ-043 were determined for 130 wild-type strains, including 60 H37Rv independent cultures and 70 diverse clinical isolates, plus 33 non-wild-type clinical strains with known BDQ susceptibility. MICs were correlated with whole-g

SUBMITTER: Ghodousi A 

PROVIDER: S-EPMC12517268 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature