A novel colistin adjuvant identified by virtual screening for ArnT inhibitors.

ABSTRACT:

Background

Colistin is a last-resort treatment option for many MDR Gram-negative bacteria. The covalent addition of l-aminoarabinose to the lipid A moiety of LPS is the main colistin resistance mechanism in the human pathogen Pseudomonas aeruginosa.

Objectives

Identification (by in silico screening of a chemical library) of potential inhibitors of ArnT, which catalyses the last committed step of lipid A aminoarabinosylation, and their validation in vitro as colistin adjuvants.

Methods

The available ArnT crystal structure was used for a docking-based virtual screening of an in-house library of natural products. The resulting putative ArnT inhibitors were tested in growth inhibition assays using a reference colistin-resistant P. aeruginosa strain. The most promising com

SUBMITTER: Ghirga F 

PROVIDER: S-EPMC7443731 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature