New anti infective, found active on resistant and persistent bacteria discovered at the Rennes University in collaboration with Olgram
In this article, the team at Rennes university has exploited a recent identification of a bacterial toxin to transform it into antibiotics active on multidrug-resistant (MDR) gram-positive and -negative bacterial pathogens. The scientific team generated a new family of peptidomimetics—cyclic heptapseudopeptides—inspired from a natural bacterial peptide and structures that can be found in the sea.
Out of all peptides studied, some are found effective against methicillin-resistant Staphylococcus aureus (MRSA) in mild and severe sepsis mouse models without exhibiting toxicity on human erythrocytes and kidney cells, zebrafish embryos or mice. These new compounds are safe at their active doses and above, without nephrotoxicity. Efficacy was also demonstrated against Pseudomonas aeruginosa and MRSA in a skin infection model. Importantly, these compounds did not result in resistance after serial passages for 2 weeks and 4 or 6 days’ exposure in vivo. Activity of those heptapseudopeptides was explained by the ability of unnatural amino acids to strengthen dynamic association with bacterial lipid bilayers.
Nicolas I, Bordeau V, Bondon A, Baudy-Floc’h M, Felden B (2019) Novel antibiotics effective against gram-positive and -negative multi-resistant bacteria with limited resistance. PLoS Biol 17(7): e3000337. https://doi.org/10.1371/journal.pbio.3000337