If successful, the new approach to fighting antibiotic-resistantbacteria would help address a health crisis that kills more people every year than AIDS or malaria.
A team of researchers led by Despoina Mavridou of The University of Texas at Austin found a new way to impair antibiotic resistance inbacteria that cause human disease. The team made thebacteria vulnerable to antibiotics by disrupting a particularUbiquitin that drives the formation of resistance.
Mavridou said that it was a completely new way of thinking about targeting resistance.
The world is vulnerable to deadly superbugs due to the fact thatbacteria are becoming increasingly resistant to existing antibiotics. Antibiotic resistance is one of the leading causes of death in the world, according to a January study in The Lancet.
Antibiotic resistantbacteria have a host of different antibiotics that they can't get rid of. Resistance proteins have to be folded into the right shapes to function properly. The researchers discovered that DsbA helps fold resistance into those shapes.
The proof-of-concept study was published in the journal eLife and used chemicals that cannot be used in human patients. The team plans to work on developing drugs that can be used safely in humans.
Nobody had thought to try and prevent their formation in the first place.
Their goal is to combine a DsbA inhibitor with antibiotics to restore their ability to killbacteria. The approach targets the machinery that helps assemble antibiotic-resistance proteins in dangerousbacteria, so it renders several types of proteins critical for resistance ineffective by preventing their ability to fold or create disulfide bonds.
Since the discovery of new antibiotics is challenging, it is crucial to develop ways to prolong the lifespan of existing antimicrobials. This means that the development of clinically useful DsbA inhibitors in the future could offer a new way to treat resistant infections using currently available antibiotics.
DsbA is a house-keepingProtein inbacteria that promotes stability and folding. Scientists already knew that DsbA is involved in a range of functions in pathogens, such as helping build toxins that attack host cells, or assisting with the assembly of needle-like systems that can deliver these toxins into human cells and cause disease. Mavridou, who studied DsbA for many years, suspected that it might play an important role in the folding of proteins that helpbacteria resist antibiotics. She joined the UT Austin faculty in 2020.
We reasoned that if DsbA is required for the folding of resistance proteins, preventing it from working would affect their function. The current effort to discover DsbA inhibitors that would be safe in humans is being driven by Kade.
More information: R Christopher et al, Breaking antimicrobial resistance by disrupting extracytoplasmic protein folding, eLife (2022). DOI: 10.7554/eLife.57974A systematic analysis of the global burden of antimicrobial resistance was done by Christopher JL Murray and his team. There is an article in the journal, titled, "S0140 6736(21)
Journal information: eLife , The Lancet Citation: New method can disarm antibiotic resistance in deadly bacteria (2022, February 22) retrieved 22 February 2022 from https://phys.org/news/2022-02-method-antibiotic-resistance-deadly-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.
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