Amphiphilic nebramine analogs synergize with β-lactam/β-lactamase inhibitor combinations, including cefepime-taniborbactam and meropenem-xeruborbactam against metallo-β-lactamase-carrying <i>Pseudomonas aeruginosa</i>.

ABSTRACT: Cefepime-taniborbactam (FEP-TAN) and meropenem-xeruborbactam (MEM-XER) are β-lactam-β-lactamase inhibitor (BL-BLI) combinations currently in development and both projected to treat metallo-β-lactamase (MBL)-producing Gram-negative pathogens. Among Gram-negative pathogens, the low permeability of the outer membrane of Pseudomonas aeruginosa poses unique challenges to drug discovery in general and to BL-BLIs in particular. This study set out to augment β-lactam antibiotic potency by enhancing outer membrane permeability of P. aeruginosa using novel amphiphilic aminoglycoside-based outer membrane permeabilizers. Amphiphilic nebramines acting as outer membrane permeabilizers, were synthesized and evaluated in combination with β-lactam antibiotics and BL-BLIs against P. aerugin

SUBMITTER: Lozeau C 

PROVIDER: S-EPMC12302231 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature