An important step has been taken in the development of a new antibiotic based teixobactin, able to eradicate many resistant bacteria.
Antibiotic resistance is a scourge promised to a great future. Already responsible for 10 million deaths, multidrug-resistant infections suggest a major health crisis, for lack of new drugs. That's why the discovery of Teixobactin in 2015 sparked enthusiasm. Isolated in the soil microbiota by a team from Northeastern University in Boston, this molecule has the potential to become an essential antibiotic.
Because teixobactin has the ability to destroy Gram + bacteria by playing with their known resistance mechanisms. Among its proven targets, many celebrities: the bacillus of tuberculosis (M. tuberculosis), the bacterium responsible for most pneumonia (S. pneumonia), or staphylococcus aureus and enterococcus, responsible for serious nosocomial infections.
Active analogues in vivo
But the development of a new medicine is a way of the cross. Before reaching the antibiotic of the future, it is still necessary to know how to produce the molecule on a large scale, in a version that is not toxic to humans. It is in this process that an important step has just been taken, as announced by a team of chemists from the University of Lincoln (United Kingdom) in an article published in the Journal of Medicinal Chemistry.
Indeed, the researchers succeeded in producing ten teixobactin analogues capable of eradicating resistant strains in the laboratory but also in vivo, on mouse corneas. Unlike the original molecule, whose synthesis is as tedious as it is random, these analogs can be manufactured in less than an hour, and seem just as active. Precious tools to hope to achieve the long-awaited new antibiotic.
At least six to ten years waiting
"Analogs are fundamental to understanding the therapeutic potential of teixobactins in humans," says Ishwar Singh, senior author, Future Science. "There is a high rate of failure when trying to transpose a molecule from the discovery stage to that of clinical use, particularly because of secondary toxicities in humans. "
Teixobactin prevents pathogenic bacteria from synthesizing the molecules (peptidoglycans) that make up their outer wall, causing their destruction. At present, no resistance mechanism has been identified. It seems that the molecule attacks mechanisms that are fairly fundamental and unlikely to mutate. But biologists are cautious, because it often takes decades of intensive use to see new resistance.
"There is still a lot of work to be done before using Teixobactin as an antibiotic in humans," says the chemist. "It will probably take six to ten years to get a drug that doctors can prescribe to their patients, but it's an important step in the right direction. "