Promising antibacterial efficacy of arenicin peptides against the emerging opportunistic pathogen Mycobacterium abscessus
Abstract 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 o...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Journal of Biomedical Science |
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| Online Access: | https://doi.org/10.1186/s12929-024-01007-8 |
| _version_ | 1797273661352181760 |
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| author | Magali Casanova Marc Maresca Isabelle Poncin Vanessa Point Hamza Olleik Céline Boidin-Wichlacz Aurélie Tasiemski Kamel Mabrouk Jean-François Cavalier Stéphane Canaan |
| author_facet | Magali Casanova Marc Maresca Isabelle Poncin Vanessa Point Hamza Olleik Céline Boidin-Wichlacz Aurélie Tasiemski Kamel Mabrouk Jean-François Cavalier Stéphane Canaan |
| author_sort | Magali Casanova |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-07T14:47:31Z |
| format | Article |
| id | doaj.art-4c8949af99094165b508fb3ee240a892 |
| institution | Directory Open Access Journal |
| issn | 1423-0127 |
| language | English |
| last_indexed | 2024-03-07T14:47:31Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biomedical Science |
| spelling | doaj.art-4c8949af99094165b508fb3ee240a8922024-03-05T19:52:24ZengBMCJournal of Biomedical Science1423-01272024-01-0131111610.1186/s12929-024-01007-8Promising antibacterial efficacy of arenicin peptides against the emerging opportunistic pathogen Mycobacterium abscessusMagali Casanova0Marc Maresca1Isabelle Poncin2Vanessa Point3Hamza Olleik4Céline Boidin-Wichlacz5Aurélie Tasiemski6Kamel Mabrouk7Jean-François Cavalier8Stéphane Canaan9CNRS, Aix-Marseille Univ, LISM UMR7255, IMM FR3479Aix Marseille Univ, CNRS, Centrale Marseille, iSm2 (UMR7313)CNRS, Aix-Marseille Univ, LISM UMR7255, IMM FR3479CNRS, Aix-Marseille Univ, LISM UMR7255, IMM FR3479Aix Marseille Univ, CNRS, Centrale Marseille, iSm2 (UMR7313)Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR9017 - CIIL - Center for Infection and Immunity of LilleUniv. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR9017 - CIIL - Center for Infection and Immunity of LilleAix-Marseille Univ, CNRS, UMR7273, ICRCNRS, Aix-Marseille Univ, LISM UMR7255, IMM FR3479CNRS, Aix-Marseille Univ, LISM UMR7255, IMM FR3479Abstract 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.https://doi.org/10.1186/s12929-024-01007-8Mycobacterial infectionCystic fibrosisHemolytic activityPore forming activityElectron microscopyAntibiotic resistance |
| spellingShingle | Magali Casanova Marc Maresca Isabelle Poncin Vanessa Point Hamza Olleik Céline Boidin-Wichlacz Aurélie Tasiemski Kamel Mabrouk Jean-François Cavalier Stéphane Canaan Promising antibacterial efficacy of arenicin peptides against the emerging opportunistic pathogen Mycobacterium abscessus Journal of Biomedical Science Mycobacterial infection Cystic fibrosis Hemolytic activity Pore forming activity Electron microscopy Antibiotic resistance |
| title | Promising antibacterial efficacy of arenicin peptides against the emerging opportunistic pathogen Mycobacterium abscessus |
| title_full | Promising antibacterial efficacy of arenicin peptides against the emerging opportunistic pathogen Mycobacterium abscessus |
| title_fullStr | Promising antibacterial efficacy of arenicin peptides against the emerging opportunistic pathogen Mycobacterium abscessus |
| title_full_unstemmed | Promising antibacterial efficacy of arenicin peptides against the emerging opportunistic pathogen Mycobacterium abscessus |
| title_short | Promising antibacterial efficacy of arenicin peptides against the emerging opportunistic pathogen Mycobacterium abscessus |
| title_sort | promising antibacterial efficacy of arenicin peptides against the emerging opportunistic pathogen mycobacterium abscessus |
| topic | Mycobacterial infection Cystic fibrosis Hemolytic activity Pore forming activity Electron microscopy Antibiotic resistance |
| url | https://doi.org/10.1186/s12929-024-01007-8 |
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