“Novel antibiotics effective against gram-positive and -negative multi-resistant bacteria with limited resistance”

BREAKTHROUGH RESEARCH ARTICLE in PLoS – Biology

“Novel antibiotics effective against gram-positive and -negative multi-resistant bacteria with limited resistance”

Irène Nicolas, Valérie Bordeau, Arnaud Bondon, Michèle Baudy-Floc’h, BriceFelden 

Received: April 23, 2019; Accepted: June 6, 2019; Published: July 9, 2019

“…We generated a new family of peptidomimetics – cyclic heptapseudopeptides – inspired from a natural bacterial peptide. Out of the 4 peptides studied, 2 are 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, and 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 mouse skin infection model. Importantly, these compounds did not result in resistance after serial passages for 2 weeks and 4 or 6 days’ exposure in mice.

“Activity of heptapseudopeptides was explained by the ability of unnatural amino acids to strengthen dynamic association with bacterial lipid bilayers and to induce membrane permeability, leading to bacterial death. Based on structure determination, we showed that cationic domains surrounded by an extended hydrophobic core could improve bactericidal activity. Because 2 peptide analogs, Pep 16 and Pep19, are effective against both MRSA and P. aeruginosa in severe sepsis and skin infection models, respectively, we believe that these peptidomimetics are promising lead candidates for drug development. We have identified potential therapeutic agents that can provide alternative treatments against antimicrobial resistance.

“Because the compounds are potential leads for therapeutic development, the next step is to start phase I clinical trials.” – END OF EXCERPT in https://ireallyappreciatescience.com

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Copyright: © 2019 Nicolas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting information files.

Funding: This research was funded by l’Agence Nationale pour la Recherche (ANR-15-CE12-0003-01, “sRNA-Fit”) to BF, la “Fondation pour la Recherche Médicale” (DBF20160635724, “Bactéries et champignons face aux antibiotiques et antifongiques”) to BF, and Ouest-Valorisation, Société d’Accélération du Transfert de Technologies to BF. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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