Conjugation of Polycationic Peptides Extends the Efficacy Spectrum of β-Lactam Antibiotics.

ABSTRACT: Antibiotic-resistant enterococci represent a significant global health challenge. Unfortunately, most β-lactam antibiotics are not applicable for enterococcal infections due to intrinsic resistance. To extend their antimicrobial spectrum, polycationic peptides are conjugated to examples from each of the four classes of β-lactam antibiotics. Remarkably, the β-lactam-peptide conjugates gained an up to 1000-fold increase in antimicrobial activity against vancomycin-susceptible and vancomycin-resistant enterococci. Even against β-lactam-resistant Gram-negative strains, the conjugates are found to be effective despite their size exceeding the exclusion volume of porins. The extraordinary gain of activity can be explained by an altered mode of killing. Of note, the conjugates showed a concentrat

SUBMITTER: Werner J 

PROVIDER: S-EPMC11672299 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature