Opening up the world around us to next-generation antibiotics

An international research team has found nearly a million potential sources of antibiotics in the natural world.

Research published in the journal Cell by a team including QUT computational biologist Associate Professor Luis Pedro Coelho has used machine learning to identify 863,498 promising antimicrobial peptides – small molecules that can kill or inhibit the growth of infectious microbes.

The study’s findings come amid a renewed global focus on combating antimicrobial resistance (AMR) as humanity grapples with the growing number of superbugs resistant to current drugs.

“There is an urgent need for new methods for antibiotic discovery,” said Professor Coelho, researcher at the QUT Center for Microbiome Research. The center studies the structure and function of microbial communities from around the world.

“It is one of the greatest threats to public health, killing 1.27 million people every year.”

Associate Professor Luis Pedro Coelho

Without intervention, AMR is estimated to cause up to 10 million deaths per year by 2050.

“Using artificial intelligence to understand and harness the power of the global microbiome will hopefully drive innovative research for better public health outcomes,” he said.

The team verified the machine predictions by testing 100 laboratory-made peptides against clinically significant pathogens. They found 79 disrupted bacterial membranes and 63 specifically targeted antibiotic-resistant bacteria such as Staphylococcus aureus and Escherichia coli.

“In addition, some peptides helped eliminate infections in mice; two in particular reduced bacteria by up to four orders of magnitude,” said Professor Coelho.

In a preclinical model tested on infected mice, treatment with these peptides produced results comparable to the effects of polymyxin B – a commercially available antibiotic used to treat meningitis, pneumonia, sepsis and urinary tract infections.

To obtain these results, more than 60,000 metagenomes (a collection of genomes within a specific environment), which together contain the genetic makeup of more than a million organisms, were analyzed. They came from sources around the world, including the marine and soil environments, and the guts of humans and animals.

The resulting AMPSphere – a comprehensive database of these new peptides – has been published as a publicly available, open-access resource for the discovery of new antibiotics.

Professor Coelho’s research was conducted as part of his ARC Future Fellowship through the QUT School of Biomedical Science, in collaboration with the Cesar de la Fuente Laboratory at the University of Pennsylvania, Fudan University, the European Molecular Biology Laboratory and APC Microbiome Ireland .

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