New, effective antibiotic does not trigger resistance in mice

In the search for alternatives to effective antibiotics that do not trigger antibiotic resistance, Nicolas and his colleagues reported two new molecules effective against gram-positive and negative multidrug-resistant bacteria. And, importantly, the new antibiotics do not appear to cause toxicity or resistance to resistance when used to treat an infection in mice, according to a new article published July 9 in PLOS Biology (1).

Antibiotics can save lives, however, overuse has led to dangerous resistance to antibiotics and the emergence of superbugs. According to the World Health Organization (WHO), antibiotic resistance is one of the greatest threats to global health. Although it can occur naturally, it is accelerated by the misuse of antibiotics in both animals and animals.

The number of deaths from methicillin-resistant S. aureus (MRSA) is increasing every year, and by 2050 it is estimated that at least 10 million people will die each year as a result of antimicrobial resistance. Unfortunately, there is little incentive for pharmaceutical companies to invest the enormous amounts needed to develop new antibiotics against these strains. As a result, the current clinical pipeline is currently dominated by established clbad derivatives of "me too" compounds.

The team of researchers from the National Institute of Health and Medical Research (INSERM) and the University of Rennes has come up with a new clbad of molecules that could potentially change all that. The new molecules are actually bacterial toxins themselves turned into potent antibiotics against various Gram positive or negative bacteria, responsible for human infections. The discovery was made in 2011, when scientists identified for the first time a molecule that was both toxic and antibiotic.

"We understood that a toxin produced by Staphylococcus aureus, whose role is to facilitate the infection, is also able to kill other bacteria present in our body," says Professor Brice Felden, director of the research laboratory on RNA and bacterial medicine in Rennes. "We had identified a molecule that was both toxic and antibiotic. We thought that if we could separate these activities, we could create a new non-toxic antibiotic for the body. A challenge that we accepted!

The peptidomimetics are based on existing natural bacterial peptides but have been shortened and modified to be effective against two resistant bacteria. Staphylococcus aureus and Pseudomonas aeruginosa in murine models of severe sepsis or skin infection. In addition, the molecules caused damage to the mice, even at higher doses – similar drugs can damage the kidneys. Importantly, the bacteria showed no signs of resistance after several days of contact with the antibiotics. But the results should be approached with caution because of the short study period of only 15 days.

The new discovery offers the opportunity to fight against antibiotic resistance worldwide. "We have identified potential therapeutic agents that can provide alternative treatments for antimicrobial resistance," write the authors. "Since compounds are potential leads for therapeutic development, the next step is to start phase I clinical trials."

(1) Nicolas, I. et al. New antibiotics effective against multidrug resistant and negative bacteria with limited resistance. PLOS Biology (2019). DOI: 10.1371 / journal.pbio.3000337