Medical Research Council - London Institute of Medical Sciences

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Folding Up

Blocking a bacterial protein Dsb2 in resistant strains restores sensitivity to antibiotics

02 April 2022

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

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