Loss-of-Function Mutations in the Penicillin-Binding Protein PonA1 Confer Agar-Dependent Resistance to Durlobactam in Mycobacterium abscessus.

ABSTRACT: Background: Infections caused by the multidrug-resistant pathogen Mycobacterium abscessus (Mab) are notoriously difficult to treat. The novel β-lactamase inhibitor durlobactam, in combination with β-lactams, shows potent bactericidal activity against Mab, but the potential for acquired resistance remains a clinical concern. Objectives: To identify and characterize mechanisms of acquired resistance to durlobactam in Mab. Methods: In vitro single-step resistance selection was performed by plating wild-type Mab ATCC 19977 and by transcriptional silencing using a CRISPR interference (CRISPRi) system. Minimum inhibitory concentrations (MICs) were determined by both an agar-based method and broth microdilution. Results: Whole-genome

SUBMITTER: Negatu DA 

PROVIDER: S-EPMC12837516 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature