Unlocking the world around us for next-gen antibiotics

Publicly released:
Australia; QLD
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An international research team has found almost a million potential sources of antibiotics in the natural world.

Media release

From: Queensland University of Technology (QUT)

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 findings of the study come with a renewed global focus on combatting antimicrobial resistance (AMR) as humanity contends with the growing number of superbugs resistant to current drugs.

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

“It is one of the top public health threats, killing 1.27 million people each year.”

Without intervention, it is estimated that AMR could 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.

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

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

More than 60,000 metagenomes (a collection of genomes within a specific environment), which together contained the genetic makeup of over one million organisms, were analysed to get these results. They came from sources across the globe including marine and soil environments, and human and animal guts.

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

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.

For a copy of the QUT media release, manuscript, images and video, please contact lauren.baxter@qut.edu.au with a confirmation of agreement to the embargo.

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Luis Pedro Coelho
Luis Pedro Coelho
Luis Pedro Coelho
Luis Pedro Coelho
Journal/
conference:
Cell
Research:Paper
Organisation/s: Queensland University of Technology (QUT)
Funder: This work was partly funded by the EMBL and the following grants: National Natural Science Foundation of China grants T2225015 and 61932008 (L.P.C. and X.-M.Z.); Shanghai Science and Technology Commission Program grant 23JS1410100 (L.P.C. and X.-M.Z.); National Key R&D Program of China grants 2023YFF1204800 and 2020YFA0712403 (L.P.C. and X.-M.Z.); Shanghai Municipal Science and Technology Major Project grant 2018SHZDZX01 (L.P.C. and X.-M.Z.); Lingang Laboratory and National Key Laboratory of Human Factors Engineering Joint Grant LG-TKN- 202203-01 (X.-M.Z.); The Science and Technology Commission of Shanghai Municipality grant 22JC1410900 (L.P.C.); Australian Research Council grant FT230100724 (L.P.C.); the Langer Prize from the AIChE Foundation (C.d.l.F.-N.); National Institutes of Health grantR35GM138201 (C.d.l.F.-N.); Defense Threat Reduction Agency grantsHDTRA11810041, HDTRA1-21-1-0014, and HDTRA1-23-1-0001 (C.d.l.F.-N.); PID2021-127210NB-I00, MCIN/AEI/ Q12 10.13039/501100011033/FEDER, UE (J.H.-C.); ’la Caixa’ Foundation ID 100010434, fellowship code LCF/BQ/DI18/11660009 (A.R.d.R.); and the European Union’s Horizon 2020 research and innovation program under the Marie Sk1odowska-Curie grant agreement 713673 (A.R.d.R.).
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