New antibiotics are being tested
Antibiotics have saved millions of lives during their existence and are considered one of the most important achievements of modern medicine. Unfortunately, the resistance of bacteria gradually makes them ineffective and carries the threat of catastrophic consequences for public health. The few new antibiotics that enter the market are mostly derived from existing antibiotics.
Professor Bryce Felden and his colleagues from the French National Institute of Health and Medical Research (Institut national de la santé et de la recherche médicale, Inserm) and the University of Rennes (Université de Rennes) identified a new bacterial toxin, on the basis of which they created potent antibiotics active against gram-positive and gram-negative bacteria.
In 2011, a toxin produced by Staphylococcus aureus to facilitate infection was discovered, which is also capable of killing other bacteria present in the body. This molecule had both toxic and antibacterial properties. The authors decided to separate these effects and create a new antibiotic that is safe for the body.
A new family of so–called peptidomimetics has been synthesized - these are cyclic heptapseudopeptides consisting of seven amino acids. They are similar to natural bacterial peptides, but have been shortened and modified. Of the twenty molecules created, two were effective against antibiotic-resistant Staphylococcus aureus and Pseudomonas aeruginosa. This has been proven in mouse models of severe sepsis or skin infection. Toxicity to other cells and organs was not observed in either animals or humans. The new antibiotics are well tolerated in active doses and do not have the toxic effect on the kidneys characteristic of this type of compounds. Even at a dosage exceeding the effective dose by 10-50 times, no toxic effect was detected.
It is important to note that the bacteria that had been in contact with the new antibiotics for several days in vivo showed no signs of resistance. In addition, the researchers deliberately created conditions favorable for the development of resistance in vitro and in vivo, but even then it did not form. However, it is necessary to take into account the short time of experiments (up to 15 days).
The antibacterial activity of peptidomimetics is partly due to the ability of non-native amino acids to enhance attachment to bacterial cell membranes. This leads to increased membrane permeability and bacterial death.
The authors of the study consider the new molecules to be a promising substance for the development of new antibiotics that can defeat antimicrobial-resistant bacteria.
The next stage is the launch of the first phase of human clinical trials.
A patent for the invention has been obtained.
Article I. Nicolas et al. Novel antibiotics effective against gram-positive and -negative multi-resistant bacteria with limited resistance is published in the journal Plos Biology.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on Inserm: New Antibiotics Developed by Inserm and Université de Rennes 1.