Study unlocks key to success of drug-resistant bacteria

Researchers have discovered how Gram-negativebacteria, which cause drug-resistant pneumonia, bloodstream infections, and surgical site infections in hospitalized patients, build a crucial component of their outer membrane that shields them from attacks by the immune system and antibiotics. The new findings could lead to the development of novel drugs to fight these potentially deadlybacteria, the source of countless infections in health care settings worldwide.

The study was published in Nature.

We knew that Gram-negativebacteria have two main components,lipids and sugars, which together form an impermeable barrier. Filippo Mancia, a co-leader of the study and professor of cellular biophysics at Columbia University Vagelos College of Physicians and Surgeons, says that the missing link was how this lipopolysaccharide component comes together.

Mancia and colleagues were able to determine the structures of the O-antigen ligase in two different functional configurations using cutting-edge single-particle cryo- electron microscopy. The team learned how the enzyme positions the sugars and lipids so that they can combine to form a protective barrier.

If you could block the assembly of the lipopolysaccharide component, the Gram-negativebacteria would be more vulnerable to the immune system.

This means that we would have many opportunities to disrupt the membrane, not just at one stage of the bacteria's life.

The structure of the last step in assembling lipopolysaccharide barriers in drug-resistantbacteria may be revealed by the researchers.

TheStructural basis of lipopolysaccharide maturation by the O-antigen ligase is the subject of a paper.

More information: Khuram U. Ashraf et al, Structural basis of lipopolysaccharide maturation by the O-antigen ligase, Nature (2022). DOI: 10.1038/s41586-022-04555-x Journal information: Nature Citation: Study unlocks key to success of drug-resistant bacteria (2022, April 8) retrieved 8 April 2022 from https://phys.org/news/2022-04-key-success-drug-resistant-bacteria.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.