Folding Up

Antibiotic resistance is a growing crisis, making bacterial infections increasingly challenging to treat. While finding new antibiotics or targeting specific resistance pathways provides limited solutions, disrupting general mechanisms underpinning antibiotic resistance could be more promising. Gram-negative bacteria, including Salmonella and Escherichia coli, have a multi-layered cell envelope harbouring important classes of antibiotic-resistant proteins. To function properly, many need assistance from DsbA, another protein that helps them fold into correct shapes, by establishing chemical links known as disulphide bonds between particular amino acids. Recent research found that blocking this process restored the effectiveness of existing antibiotics against multiple resistant bacteria, such as Klebsiella pneumoniae, unharmed after exposure to antibiotics alone (left), but destroyed by a combination of antibiotics and a DsbA inhibitor (right). In caterpillars infected with resistant bacteria, antibiotics dramatically boosted survival only if those bacteria lacked DsbA, suggesting that targeting protein folding alongside antibiotics could help defeat resistant infections.

Written by Emmanuelle Briolat

Emmanuelle Briolat

Writer

A researcher specialising in visual signals in Lepidoptera, camouflage and the effects of light pollution, Emmanuelle’s writing covers a range of topics, from biomedical research to children’s books about moth defences.

Website

• Image from work by R Christopher D Furniss and Nikol Kaderabkova, and colleagues
• MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London, UK
• Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)
• Published in eLife, January 2022