Semisynthetic polymyxins with potent antibacterial activity and reduced kidney cell toxicity.

ABSTRACT: The growing incidence of infections caused by multi-drug resistant Gram-negative bacteria has led to an increased use of last-resort antibiotics such as the polymyxins. Polymyxin therapy is limited by toxicity concerns, most notably nephrotoxicity. Recently we reported the development of a novel class of semisynthetic polymyxins with reduced toxicity wherein the N-terminal lipid and diaminobutyric acid residue are replaced by a cysteine-linked lipid featuring a reductively labile disulfide bond. In the present study we further explored the potential of this approach by also varying the amino acid residue directly adjacent to the polymyxin macrocycle. This led to the identification of new semisynthetic polymyxins that maintain the potent antibacterial activity of the clinically used polymyx

SUBMITTER: Slingerland CJ 

PROVIDER: S-EPMC10650952 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature