"Last Resort" Antibiotic Pops Bacteria Like Balloons
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Last resort' antibiotic pops bacteria like balloons:
The antibiotic colistin has become a last resort treatment for infections caused by some of the world's nastiest superbugs. However, despite being discovered over 70 years ago, the process by which this antibiotic kills bacteria has, until now, been something of a mystery.
Now, researchers have revealed that colistin punches holes in bacteria, causing them to pop like balloons. The work, funded by the Medical Research Council and Wellcome Trust, and published in the journal eLife, also identified a way of making the antibiotic ;more effective at killing bacteria.
Colistin was first described in 1947, and is one of the very few antibiotics that is active against many of the most deadly superbugs, including E. coli, which causes potentially lethal infections of the bloodstream, and Pseudomonas aeruginosa and Acinetobacter baumannii, which frequently infect the lungs of people receiving mechanical ventilation in intensive care units.
These superbugs have two skins called membranes. Colistin punctures both membranes, killing the bacteria. However, whilst 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 from Imperial's Department of Infectious Disease [has] shown that colistin also targets LPS in the inner membrane, even though there's very little of it present.
[...] Dr Edwards said: "It sounds obvious that colistin would damage both membranes in the same way, but it was always assumed colistin damaged the two membranes in different ways. There's so little LPS in the inner membrane that it just didn't seem possible, and we were very sceptical at first. However, by changing the amount of LPS in the inner membrane in the laboratory, and also by chemically modifying it, we were able to show that colistin really does puncture both bacterial skins in the same way - and that this kills the superbug."
Journal Reference:
Akshay Sabnis, Katheryn LH Hagart, Anna Klockner, et al. Colistin kills bacteria by targeting lipopolysaccharide in the cytoplasmic membrane, (DOI: 10.7554/eLife.65836)
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