Evolved resistance to a novel cationic peptide antibiotic requires high mutation supply.

ABSTRACT:

Background and objectives

A key strategy for resolving the antibiotic resistance crisis is the development of new drugs with antimicrobial properties. The engineered cationic antimicrobial peptide WLBU2 (also known as PLG0206) is a promising broad-spectrum antimicrobial compound that has completed Phase I clinical studies. It has activity against Gram-negative and Gram-positive bacteria including infections associated with biofilm. No definitive mechanisms of resistance to WLBU2 have been identified.

Methodology

Here, we used experimental evolution under different levels of mutation supply and whole genome sequencing (WGS) to detect the genetic pathways and probable mechanisms of resistance to this peptide. We propagated populations of wild-type and hypermutator Pseudomon

SUBMITTER: Santos-Lopez A 

PROVIDER: S-EPMC9198447 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature