Can antibiotic resistance finally be defeated? – DW – 06/06/2024

Antibiotic-resistant infections kill millions of people each year. They have the potential to take us back to the Middle Ages, when common infections such as urinary tract infections or pneumonia were lethal and untreatable.

Antimicrobial resistance (AMR) occurs when germs that cause infections – bacteria, viruses or fungi – develop ways to evade the drugs used to treat them.

The overuse of antibiotics, in places such as poultry farms and health clinics, has become one of the main drivers of the problem.

The good news is that significant progress is being made in the matter. The problem of “antibiotic resistance is far from being solved, but much progress has been made, both in the understanding and in the practices for discovering new antibiotics,” says Luis Pedro Coelho, a computational biologist at the Queensland University of Technology, in Australia.

Coelho led a new study published in the journal cellwhich features a huge database of nearly a million potential antibiotic compounds.

According to Sebastian Hiller, a structural biologist at the University of Basel in Switzerland, who was not involved in the research, “this is just one example of ongoing research showing that our scientific ability to fight superbugs is enormous.”

With the help of artificial intelligence

The study used machine learning to search for potential antibiotic agents in a huge database of microbes that live in environments such as soil, ocean, and human and animal viscera.

“Bacteria constantly fight each other in these environments, using tools called peptides. The researchers looked for antibiotic peptides in this space and found some hidden gems,” explains Hiller.

The algorithm examined billions of possible protein sequences and narrowed them down to the top candidates with predicted antimicrobial actions.

In total, 863,498 new antimicrobial peptides were predicted, more than 90 percent of which had not been described before.

According to Coelho, all peptides have the same general mechanism of action to kill bacteria: crossing cell membranes that protect them from the environment.

“We also observed that some peptides are more effective against certain bacterial strains than others, but we still cannot explain exactly why, nor predict which peptide will work against which bacteria,” Coelho stated.

The effectiveness of peptide antibiotics

To find out which of these peptides could be useful as antibiotics, the researchers synthesized 100 of them and tested them against 11 disease-causing bacterial strains.

They found that 79 peptides disrupted bacterial membranes and that 63 specifically targeted antibiotic-resistant bacteria, such as Escherichia coli (E.coli) and Staphylococcus aureus.

“This indicates that their effectiveness may be limited in living beings. Still, this is a remarkable result, and the compounds could avoid the serious toxic side effects of antibiotics used as a last resort such as polymyxins,” said Seyed Majed Modaresi. , from the University of Basel, who was also not involved in the study.

Is there reason for optimism?

The researchers also tested the compounds on mice with infected skin abscesses, but only three of the peptides showed antimicrobial effects on them.

The authors published their data set with open access, allowing other scientists to review the 863,498 peptides and develop antibiotic drugs with specific uses in mind.

For example, one could try to minimize the effects of antibiotics on the bacterial flora beneficial to humans. The data could also be used to produce antibiotics against which bacteria have not developed resistance.

For Hiller, although there are reasons to be optimistic, the next big challenge is to create new antibiotic agents that are commercially viable. “We only use new antibiotics when the old ones no longer work. This is good as it prevents bacteria from developing resistance to them, but it means they are not economically viable,” she explained.

(ers/rml)