Researchers have revealed how an ̵
The results from Imperial College London and the University of Texas may also reveal a potential way to make antibiotics more powerful.
The antibiotic colistin has become a last resort treatment for infections caused by some of the world’s most disgusting superbugs. Despite being discovered over 70 years ago, the process by which this antibiotic kills bacteria has so far been something of a mystery.
Now, researchers have revealed that colistin punctures holes in bacteria and causes them to pop out like balloons. The work, funded by the Medical Research Council and the Wellcome Trust, and published in the journal eLife, also identified a way to make antibiotics more effective at killing bacteria.
Colistin was first described in 1947 and is one of the very few antibiotics active against many of the most deadly superbugs, including E. coli, which causes potentially fatal infections in the bloodstream, and Pseudomonas aeruginosa and Acinetobacter baumannii, which are often infects the lungs of people receiving mechanical ventilation in intensive care units.
These superbugs have two ‘skins’, called membranes. Colistin punctures both membranes and kills the bacteria. However, while it was known that colistin damaged the outer membrane by targeting a chemical called lipopolysaccharide (LPS), it was unclear how the inner membrane was pierced.
Now a team led by Dr. Andrew Edwards of the Imperial’s Department of Infectious Disease showed that colistin also targets LPS in the inner membrane, although very little of it is present.
Dr. Edwards said: “It sounds obvious that colistin would damage both membranes in the same way, but it was always assumed that colistin damaged the two membranes in different ways. There is so little LPS in the inner membrane that it just did not seem possible. , and we were very skeptical at first.But by changing the amount of LPS in the inner membrane of the laboratory and also by modifying it chemically we could show that colistin really punctures both bacterial skins in the same way – and that this kills superbug . “
Then the team decided to see if they could use this new information to find ways to make colistin more effective at killing bacteria.
They focused on a bacterium called Pseudomonas aeruginosa, which also causes serious lung infections in people with cystic fibrosis. They found that a new experimental antibiotic, called murepavadin, caused an accumulation of LPS in the bacterium’s inner skin, making it much easier for colistin to puncture it and kill the bacteria.
The team says that since wallpavadin is an experimental antibiotic, it cannot be used routinely in patients yet, but clinical trials are about to begin. If these attempts are successful, it may be possible to combine murepavadin with colistin to perform a potent treatment for a wide range of bacterial infections.
Akshay Sabnis, lead author of the work also from the Department of Infectious Diseases, said: “As the global crisis of antibiotic resistance continues to accelerate, colistin is becoming more and more important as the last chance to save the lives of patients infected with superbugs. By revealing how this ancient antibiotic works, we were able to come up with new ways to make it kill bacteria even more effectively and increase our arsenal of weapons against the world’s superbugs. ”
Threat to ‘nightmare bacteria’ with resistance to last resort antibiotic colistin
Provided by Imperial College London
Citation: ‘Last resort’ antibiotic pops bacteria like balloons (2021, May 4) retrieved May 4, 2021 from https://phys.org/news/2021-05-resort-antibiotic-bacteria-balloons.html
This document is subject to copyright. Except for any fair trade for the purpose of private investigation or research, no parts may be reproduced without written permission. The content is provided for informational purposes only.