Serendipitous Discovery of a Highly Active and Selective Resistance-Modifying Agent for Colistin-Resistant Gram-Negative Bacteria.

ABSTRACT: Antibiotic resistance is a growing global health concern. Colistin is one of the last-resort antibiotics that treats multidrug-resistant (MDR) Gram-negative bacterial infection. However, bacteria resistant to colistin have become increasingly prevalent. Using a bacterial whole-cell screen of a fragment-based library, one compound was discovered to resensitize MDR Escherichia coli AR-0493 to colistin with low mammalian toxicity. Interestingly, postscreening validation studies identified a highly related yet distinct compound as the actual substance responsible for the activity. Further studies showed that this novel resistance-modifying agent is not only very potent but also highly selective to potentiate the activity of polymyxin family antibiotics in a wide range of MDR Gram-negati

SUBMITTER: Gao Y 

PROVIDER: S-EPMC9016814 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature