- 作者: Magali Casanova, Marc Maresca, Isabelle Poncin, Vanessa Point, Hamza Olleik, Céline Boidin-Wichlacz, Aurélie Tasiemski, Kamel Mabrouk, Jean-François Cavalier & Stéphane Canaan
- 作者服務機構: 1.Aix Marseille Univ, CNRS, Centrale Marseille, iSm2 (UMR7313), Marseille, France 2.Aix-Marseille Univ, CNRS, UMR7273, ICR, 13013, Marseille, France 3.CNRS, Aix-Marseille Univ, LISM UMR7255, IMM FR3479, Marseille, France 4.Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR9017 - CIIL - Center for Infection and Immunity of Lille, 59000, Lille, France
- 中文摘要:
- 英文摘要:
Background
Mycobacterium abscessus, a fast-growing non-tuberculous mycobacterium, is an emerging opportunistic pathogen responsible for chronic bronchopulmonary infections in people with respiratory diseases such as cystic fibrosis (CF). Due to its intrinsic polyresistance to a wide range of antibiotics, most treatments for M. abscessus pulmonary infections are poorly effective. In this context, antimicrobial peptides (AMPs) active against bacterial strains and less prompt to cause resistance, represent a good alternative to conventional antibiotics. Herein, we evaluated the effect of three arenicin isoforms, possessing two or four Cysteines involved in one (Ar-1, Ar-2) or two disulfide bonds (Ar-3), on the in vitro growth of M. abscessus.
Methods
The respective disulfide-free AMPs, were built by replacing the Cysteines with alpha-amino-n-butyric acid (Abu) residue. We evaluated the efficiency of the eight arenicin derivatives through their antimicrobial activity against M. abscessus strains, their cytotoxicity towards human cell lines, and their hemolytic activity on human erythrocytes. The mechanism of action of the Ar-1 peptide was further investigated through membrane permeabilization assay, electron microscopy, lipid insertion assay via surface pressure measurement, and the induction of resistance assay.
Results
Our results demonstrated that Ar-1 was the safest peptide with no toxicity towards human cells and no hemolytic activity, and the most active against M. abscessus growth. Ar-1 acts by insertion into mycobacterial lipids, resulting in a rapid membranolytic effect that kills M. abscessus without induction of resistance.
Conclusion
Overall, the present study emphasized Ar-1 as a potential new alternative to conventional antibiotics in the treatment of CF-associated bacterial infection related to M. abscessus. - 中文關鍵字:
- 英文關鍵字: Mycobacterial infection, Cystic fbrosis, Hemolytic activity, Pore forming activity, Electron microscopy, Antibiotic resistance, Bactericidal activity, Antimicrobial peptide