When the Frenchman Ernest Duchesne found penicillin in 1897 and Alexander Fleming rediscovered it in 1928, the health of humanity took a giant step forward. For the first time, the chances of dying from an infection dropped dramatically. However, the use and abuse of antibiotics over the last 100 years has taught microbial pathogens to develop defenses against the best pharmacological weapon. Every year, according The Lancet, almost five million people die from microorganisms resistant to current antibiotics and it is essential to find new effective molecules. In this unavoidable fight, the laboratories of the Spanish César de la Fuente at the University of Pennsylvania and Portuguese Luis Pedro Coelho at the Queensland University of Technology have discovered, as published in cell, the world’s largest quarry (863,498 peptides) of antimicrobials from which new treatments can be developed.
Researchers have turned to artificial intelligence and machine learning (machine learning) to search anywhere—in the human body (saliva or skin), animals (pig intestines or corals), plants, land, water or extinct beings—for a combination of amino acids that have antibiotic potential. This is what is known as microbial dark matter, microorganisms that have left genetic material in any medium, but that have not yet been grown in the laboratory.
Of the almost million molecules found, nine out of 10 are unpublished and have had to be named, such as lachnospirin and enterococcina, the most effective. “They had never been described,” highlights De la Fuente. Of that huge amount, they have managed to test a hundred at a preclinical level (Petri dishes and mice) in 11 disease-causing bacterial strains, including strains resistant to antibiotics. E.coli and Staphylococcus aureus. “Our initial evaluation revealed that 63 of these candidates completely eradicated the growth of at least one of the pathogens tested and often multiple strains. In some cases, these molecules were effective against bacteria in very low doses,” explains the researcher from A Coruña, recently awarded in his country.
In a preclinical model tested in infected mice, treatment with the new peptides produced results similar to the effects of polymyxin B, a commercially available control antibiotic used to treat meningitis, pneumonia, sepsis and infections. of the urinary tract.
The fact that both researchers are biotechnologists has allowed processes that took up to a decade to be reduced to months. In this way, their teams analyzed databases of 87,920 microbial genomes and 63,410 metagenomes (mixtures of these). They were looking for combinations of amino acids unknown to pathogens that have developed resistance to current antibiotics and are responsible for what the World Health Organization considers one of the 10 main threats to humanity.
The team has published all the findings, grouped under the name AMPSphere (antimicrobial peptide sphere), on an open source platform to allow research based on its findings to any entity interested in developing new antibiotics. The idea is to overcome the pharmaceutical industry’s tendency to focus more on chronic, long-term and more profitable disease treatments.
I have spent my entire career dedicated to antibiotics, because it is one of the areas that has the least investment and that kills the most people in the world. Simply, my dream is to try to help humanity, save lives. And for me it is the most important thing, more than making money
César de la Fuente, University of Pennsylvania
“I have spent my entire career dedicated to antibiotics, because it is one of the areas that has the least investment and that kills the most people in the world. Simply, my dream is to try to help humanity, save lives. And for me it is the most important thing, more than making money,” says De la Fuente, who promotes the creation of a company that emerged from his laboratory at the University of Pennsylvania to accelerate the development of new antibiotics.
“There is an urgent need for new methods for antibiotic discovery. Using artificial intelligence to understand and harness the power of the global microbiome leads us to innovative research that improves public health,” adds Coelho, whose collaboration has been, in De la Fuente’s opinion, extraordinary.
“We are proud of this research because we believe it is the largest antibiotic discovery project ever written in terms of the amount of biological information we have explored and the amount of new molecules we have found. It is a very complete representation of all the incredible microbial diversity that exists,” highlights the Galician researcher.
De la Fuente details how the discovery comes from a novel way of approaching the global and urgent problem of resistance to antibiotics: “I think of biology as a source of information in the form of DNA, nucleotides, proteins or amino acids. . With computers we can enter as with a magnifying glass and explore all that diversity hidden from the human eye and coded in such a complex and enormous way.”
With much more humble models, other researchers work in the same direction and under the same premise: the fight against a global threat. An investigation in The Microbe, has analyzed the bacterial and archaeal communities (prokaryotic organisms that look like bacteria) in the Roman baths of the British city of Bath. “This is very exciting research. Antimicrobial resistance is recognized as one of the most important threats to global health and the search for new natural antimicrobial products is accelerating. Our study has revealed, for the first time, that some of the microorganisms present in the Roman Baths are a potential source of new antimicrobial discoveries. “Roman baths have long been considered medicinal and now, thanks to the advances of modern science, we discover that the Romans and others were right,” says Lee Hutt, lead author of the work and researcher at the University of Plymouth.
Another line of research is aimed not only at discovering new antibiotics, but also at ensuring that these do not imply unwanted effects. Treatment with the well-known amoxicillin and clindamycin causes changes in the general structure of bacterial populations in the intestine, decreasing the abundance of several beneficial microbial groups, according to a team of researchers from the University of Illinois Urbana-Champaign in Nature. Researchers have tested a new antibiotic on mice. “Lolamycin,” as the new compound is called, “does not cause any drastic changes in taxonomic composition over the cou
rse of the three-day treatment or recovery over the following 28 days,” the researchers maintain.
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