Evaluation of the Efficiency of Random and Diblock Methacrylate-Based Amphiphilic Cationic Polymers against Major Bacterial Pathogens Associated with Cystic Fibrosis.
Magali Casanova, Hamza Olleik, Slim Hdiouech, Clarisse Roblin, Jean-François Cavalier, Vanessa Point, Katy Jeannot, Baptiste Caron, Josette Perrier, Siméon Charriau, Mickael Lafond, Yohann Guillaneuf, Stéphane Canaan, Catherine Lefay, Marc Maresca
Katy Jeannot: Laboratoire Associé au CNR de la Résistance aux Antibiotiques, Centre Hospitalier Universitaire de Besançon, Boulevard Fleming, 25000 Besançon, France. ORCID
Cystic fibrosis (CF) is associated with repeated lung bacterial infection, mainly by , , and , all known to be or becoming resistant to several antibiotics, often leading to therapeutic failure and death. In this context, antimicrobial peptides and antimicrobial polymers active against resistant strains and less prompt to cause resistance, appear as a good alternative to conventional antibiotics. In the present study, methacrylate-based copolymers obtained by radical chemistry were evaluated against CF-associated bacterial strains. Results showed that the type (Random Diblock) and the size of the copolymers affected their antibacterial activity and toxicity. Among the different copolymers tested, four (i.e., Random, Random, Random, and Diblock) were identified as the most active and the safest molecules and were further investigated. Data showed that they inserted into bacterial lipids, leading to a rapid membranolytic effect and killing of the bacterial. In relation with their fast bactericidal action and conversely to conventional antibiotics, those copolymers did not induce a resistance and remained active against antibiotic-resistant strains. Finally, the selected copolymers possessed a preventive effect on biofilm formation, although not exhibiting disruptive activity. Overall, the present study demonstrates that methacrylate-based copolymers are an interesting alternative to conventional antibiotics in the treatment of CF-associated bacterial infection.
