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
Affiliations
Magali Casanova
CNRS, Aix-Marseille Univ, LISM UMR7255, IMM FR3479, 13402 Marseille, France
Hamza Olleik
Aix Marseille Univ, CNRS, Centrale Marseille, iSm2 (UMR7313), 13013 Marseille, France
Slim Hdiouech
Aix Marseille Univ, CNRS, ICR, UMR7273, 13397 Marseille, France
Clarisse Roblin
Aix Marseille Univ, CNRS, Centrale Marseille, iSm2 (UMR7313), 13013 Marseille, France
Jean-François Cavalier
CNRS, Aix-Marseille Univ, LISM UMR7255, IMM FR3479, 13402 Marseille, France
Vanessa Point
CNRS, Aix-Marseille Univ, LISM UMR7255, IMM FR3479, 13402 Marseille, France
Katy Jeannot
Laboratoire Associé au CNR de la Résistance aux Antibiotiques, Centre Hospitalier Universitaire de Besançon, Boulevard Fleming, 25000 Besançon, France
Baptiste Caron
Aix Marseille Univ, CNRS, ICR, UMR7273, 13397 Marseille, France
Josette Perrier
Aix Marseille Univ, CNRS, Centrale Marseille, iSm2 (UMR7313), 13013 Marseille, France
Siméon Charriau
Aix Marseille Univ, CNRS, Centrale Marseille, iSm2 (UMR7313), 13013 Marseille, France
Mickael Lafond
Aix Marseille Univ, CNRS, Centrale Marseille, iSm2 (UMR7313), 13013 Marseille, France
Yohann Guillaneuf
Aix Marseille Univ, CNRS, ICR, UMR7273, 13397 Marseille, France
Stéphane Canaan
CNRS, Aix-Marseille Univ, LISM UMR7255, IMM FR3479, 13402 Marseille, France
Catherine Lefay
Aix Marseille Univ, CNRS, ICR, UMR7273, 13397 Marseille, France
Marc Maresca
Aix Marseille Univ, CNRS, Centrale Marseille, iSm2 (UMR7313), 13013 Marseille, France
Cystic fibrosis (CF) is associated with repeated lung bacterial infection, mainly by Pseudomonas aeruginosa, Staphylococcus aureus, and Mycobacterium abscessus, 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 versus Diblock) and the size of the copolymers affected their antibacterial activity and toxicity. Among the different copolymers tested, four (i.e., Random10200, Random15000, Random23900, and Diblock9500) 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.