An antibiotic known as colistin is commonly used to treat infections caused by superbugs, or bacteria that have developed resistance to other more common drugs. Colistin is often used as a last resort since it is one of only a few antibiotics that are effective against resistant strains of Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii, all of which can cause lethal infections if left untreated. Although colistin was discovered in the mid-1900s, the mechanism by which it is able to kill bacteria has remained a mystery – until now.

New research performed at Imperial College London has revealed that colistin makes holes in bacteria and causes them to pop like balloons. Bacterial cells have two layers, inner and outer membranes. Colistin pierces both of these membranes by targeting specific molecules called lipopolysaccharides (LPS).

The scientists decided to see if they could use this new information to make colistin even more effective at killing superbugs. Another antibiotic called murepavadin causes an accumulation of LPS in the inner membrane of bacterial cells. The team hypothesized that more LPS would mean increased susceptibility to colistin, and that’s exactly what they saw in experiments using mice with lung infections. Colistin showed higher efficacy when dosed with murepavadin than it did on its own.

Unfortunately, murepavadin is an experimental antibiotic and cannot yet be used in patients. However, clinical trials are planned. If murepavadin is successful in these trials, it may one day be possible to combine murepavadin and colistin into a more potent treatment against bacterial infections.