Durlobactam in combination with β-lactams to combat <i>Mycobacterium abscessus</i>.

ABSTRACT: Mycobacterium abscessus (Mab) presents significant clinical challenges. This study evaluated the synergistic effects of a β-lactam and β-lactamase inhibitor combination against Mab and explored the underlying mechanisms. Synergy was assessed through MIC tests and time-kill studies, and binding affinities of nine β-lactams and BLIs to eight target receptors (L,D-transpeptidases [LDT] 1-5, D,D-carboxypeptidase, penicillin-binding protein [PBP] B, and PBP-lipo) were assessed using mass spectrometry and kinetic studies. Thermal stability and morphological changes were determined. Imipenem demonstrated high binding affinity to LDTs and PBPs, with extremely low inhibition constants (K_i,app; ≤0.002 mg/L for LDT1-2, ≤0.6 mg/L for PBPs), whil

SUBMITTER: Shin E 

PROVIDER: S-EPMC11823594 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature