Queensland researchers rediscover a 40yo antibiotic to turn the tables on the worst superbugs

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As scientists look for new ways to tackle the growing problem of drug-resistant bacteria that evolve to resist our strongest medicines, they've hit upon a new strategy: using modern-day drug analysis to re-evaluate antibiotics overlooked in the past. An antibiotic that's been forgotten since its discovery 40 years ago could now help develop new drugs against life-threatening infections caused by some of the world’s most dangerous superbugs.

University of Queensland Institute for Molecular Bioscience (IMB) researchers synthesised the antibiotic, and increased its effectiveness against extensively drug-resistant bacteria, then collaborated with Monash University to evaluate the drug using animal models of infection.

Professor Matt Cooper, Director of IMB’s Centre for Superbug Solutions, said their study, Structure, Function, and Biosynthetic Origin of Octapeptin Antibiotics Active against Extensively Drug-Resistant Gram-Negative Bacteria published in Cell Chemical Biology was prompted by the urgent need for new drugs to counter widespread resistance to last-resort treatments.

“Octapeptins were discovered in the late 1970s but were not selected for development at the time, as there was an abundance of new antibiotics with thousands of people working in antibiotic research and development,” Professor Cooper said. “Given the very few researchers left in this field now, and the sparse pipeline for new antibiotics, we’ve used modern drug discovery procedures to re-evaluate its effectiveness against superbugs.”

The researchers synthesised octapeptin and increased its effectiveness against extensively drug-resistant bacteria. They then evaluated the drug using a mouse bacteremia model with a clinical isolate of Gram-negative Pseudomonas aeruginosa.

As well as being structurally similar to colistin, scientists think the antibiotic could be less toxic to the body during treatment, based on the new analysis. And it's particularly well-suited to tackling gram-negative bacteria, responsible for conditions such as pneumonia, meningitis, bloodstream infections, and wound or surgical site infections.

“There were no new classes of antibiotics available for Gram-negative bacteria, with increasing incidence of extensive drug resistance around the world,” said Professor Cooper. “These bacteria are harder to kill as disease organisms, because they have an extra membrane to penetrate that is often hidden by a capsule or slime layer which acts to camouflage them from drugs and our immune system.”

“The emergence of resistance to meropenem, and now colistin, the antibiotic of last resort, means multi-drug and extensively drug-resistant bacteria are now a reality confronting clinicians.”

“Octapeptin showed superior antimicrobial activity to colistin against extensively resistant Gram-negative bacteria in early pre-clinical testing,” Professor Cooper said. “In addition, octapeptin was shown to be potentially less toxic to the kidneys than colistin.”

There's still a long way to go in the development and testing of this newly rediscovered antibiotic, but the researchers say it could lay the foundation for a new generation of antibiotics ready to fight life-threatening infections. With only one new class of antibiotic launched into the market in the last 30 years, we could use some more reinforcements in the ongoing fight against drug resistance.

Despite some promising research in recent years, there's no doubt it's the superbugs that have the upper hand at the moment, until we can figure out new angles of attack. Some estimates say drug-resistant infections could account for 10 million lives a year by 2050, up from 700,000 worldwide today.

"While this research is in the early stage, the rediscovery and optimisation of a forgotten drug is one way to fight back against the worst types of drug-resistant bacteria," Cooper said in October when work on the study began. "We hope that this, and similar activities in other labs, could help to repair the broken antibiotic pipeline."