Enhancing the antibacterial efficacy of vancomycin analogues: targeting metallo-β-lactamases and cell wall biosynthesis.

ABSTRACT: Vancomycin is a crucial last-resort antibiotic for tackling Gram-positive bacterial infections. However, its potency fails against the more difficult-to-treat Gram-negative bacteria (GNB). Vancomycin derivatives have shown promise as broad-spectrum antibacterials, but are still underexplored. Toward this, we present a novel strategy wherein we substitute the sugar moiety of vancomycin with a dipicolyl amine group, yielding VanNHdipi. This novel glycopeptide enhances its efficacy against vancomycin-resistant bacteria by up to 100-fold. A comprehensive approach involving microbiological assays, biochemical analyses, proteomics, and computational studies unraveled the impact of this design on biological activity. Our investigations reveal that VanNHdipi, like vancomycin, disrupts membrane-bou

SUBMITTER: Sarkar P 

PROVIDER: S-EPMC11409854 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature