An antibiotic virtually forgotten since its discovery 40 years ago could help develop new drugs against life-threatening infections caused by some of the world’s most dangerous superbugs.
What are Superbugs?
So-called “superbugs” possess antimicrobial resistance (AMR), the ability of a microbe to resist the effects of the medication used previously to treat them. These resistant microbes are difficult to treat, and require higher doses or alternative medications. Both of these options can be more expensive or more toxic.
Resistance may arise through one of three mechanisms:
- Natural resistance in certain types of bacteria.
- Genetic mutation.
- One species acquiring resistance from another.
Researchers from the University of Queensland Institute for Molecular Bioscience (IMB) synthesised the antibiotic, and increased its effectiveness against extensively drug-resistant bacteria. They then collaborated with Monash University to evaluate the drug using animal models of infection.
“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.”
According to Professor Cooper, there were no new classes of antibiotics available for Gram-negative bacteria, with increasing incidence of extensive drug resistance around the world.
“Gram-negative 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,” he said. “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.”
Colistin is an antibiotic produced by certain strains of the bacteria Paenibacillus polymyxa. Colistin is a mixture of the cyclic polypeptides colistin A and B and belongs to the class of polypeptide antibiotics known as polymyxins.
“Octapeptin showed superior antimicrobial activity to colistin against extensively resistant Gram-negative bacteria in early pre-clinical testing. In addition, octapeptin was shown to be potentially less toxic to the kidneys than colistin.”
Professor Cooper said the study laid the foundation for the development of a new generation of antibiotics to treat life-threatening infections.
Researchers from Wayne State University in Detroit, the University of Melbourne, Germany’s EMBL, and Victoria University in New Zealand collaborated on the project.
IMB research was supported by the National Health and Medical Research Council, and the US National Institute of Allergy and Infection Disease, part of the US National Institutes of Health.
You can read the study here.