biostudies-literatureUnknown15(1)Negatu DA<b>Background</b>: Infections caused by the multidrug-resistant pathogen <i>Mycobacterium abscessus</i> (<i>Mab</i>) are notoriously difficult to treat. The novel β-lactamase inhibitor durlobactam, in combination with β-lactams, shows potent bactericidal activity against <i>Mab</i>, but the potential for acquired resistance remains a clinical concern. <b>Objectives</b>: To identify and characterize mechanisms of acquired resistance to durlobactam in <i>Mab</i>. <b>Methods</b>: In vitro single-step resistance selection was performed by plating wild-type <i>Mab</i> 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. <b>Results</b>: Whole-genome Antibiotics (Basel, Switzerland)7https://www.ebi.ac.uk/biostudies/studies/S-EPMC12837516biostudies-literatureLoss-of-Function Mutations in the Penicillin-Binding Protein PonA1 Confer Agar-Dependent Resistance to Durlobactam in <i>Mycobacterium abscessus</i>.PMC12837516Aragaw WWDartois VXie MNegatu DADick TfalseLoss-of-Function Mutations in the Penicillin-Binding Protein PonA1 Confer Agar-Dependent Resistance to Durlobactam in <i>Mycobacterium abscessus</i>.<b>Background</b>: Infections caused by the multidrug-resistant pathogen <i>Mycobacterium abscessus</i> (<i>Mab</i>) are notoriously difficult to treat. The novel β-lactamase inhibitor durlobactam, in combination with β-lactams, shows potent bactericidal activity against <i>Mab</i>, but the potential for acquired resistance remains a clinical concern. <b>Objectives</b>: To identify and characterize mechanisms of acquired resistance to durlobactam in <i>Mab</i>. <b>Methods</b>: In vitro single-step resistance selection was performed by plating wild-type <i>Mab</i> 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. <b>Results</b>: Whole-genome 2025-01-01T00:00:00Z2025 Dec2026-06-15T03:14:18.89Z2026-06-15T03:08:54.791ZS-EPMC128375164159404510.3390/antibiotics15010007