Cyclophostin and Cyclipostins analogues counteract macrolide-induced resistance mediated by erm(41) in Mycobacterium abscessus.

Autor: Sarrazin M; CNRS, LISM UMR7255, IMM-FR3479, Aix-Marseille Univ, Marseille, France., Poncin I; CNRS, LISM UMR7255, IMM-FR3479, Aix-Marseille Univ, Marseille, France., Fourquet P; INSERM, CNRS, Institut Paoli-Calmettes, CRCM, Aix-Marseille Univ, Marseille Protéomique, France., Audebert S; INSERM, CNRS, Institut Paoli-Calmettes, CRCM, Aix-Marseille Univ, Marseille Protéomique, France., Camoin L; INSERM, CNRS, Institut Paoli-Calmettes, CRCM, Aix-Marseille Univ, Marseille Protéomique, France., Denis Y; Plateforme Transcriptome, Aix-Marseille Univ, CNRS, IMM-FR3479, Marseille, France., Santucci P; CNRS, LISM UMR7255, IMM-FR3479, Aix-Marseille Univ, Marseille, France., Spilling CD; Department of Chemistry and Biochemistry, University of Missouri St. Louis, St. Louis, MO, USA., Kremer L; Centre National de la Recherche Scientifique UMR 9004, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier, 34293, Montpellier, France.; INSERM, Institut de Recherche en Infectiologie de Montpellier, 34293, Montpellier, France., Moigne VL; Université Paris-Saclay, UVSQ, INSERM, Infection et Inflammation, Montigny-le-Bretonneux, France., Herrmann JL; Université Paris-Saclay, UVSQ, INSERM, Infection et Inflammation, Montigny-le-Bretonneux, France.; Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Ile-de-France Ouest, GHU Paris-Saclay, Hôpital Raymond Poincaré, Garches, France., Cavalier JF; CNRS, LISM UMR7255, IMM-FR3479, Aix-Marseille Univ, Marseille, France., Canaan S; CNRS, LISM UMR7255, IMM-FR3479, Aix-Marseille Univ, Marseille, France. canaan@imm.cnrs.fr.
Jazyk: angličtina
Zdroj: Journal of biomedical science [J Biomed Sci] 2024 Dec 03; Vol. 31 (1), pp. 103. Date of Electronic Publication: 2024 Dec 03.
DOI: 10.1186/s12929-024-01091-w
Abstrakt: Background: Mycobacterium abscessus is an emerging pathogen causing severe pulmonary infections, particularly in individuals with underlying conditions, such as cystic fibrosis or chronic obstructive pulmonary disease. Macrolides, such as clarithromycin (CLR) or azithromycin (AZM), represent the cornerstone of antibiotherapy against the M. abscessus species. However, prolonged exposure to these macrolides can induce of Erm(41)-mediated resistance, limiting their spectrum of activity and leading to therapeutic failure. Therefore, inhibiting Erm(41) could thwart this resistance mechanism to maintain macrolide susceptibility, thus increasing the rate of treatment success. In our previous study, the Erm(41) methyltransferase was identified as a possible target enzyme of Cyclipostins and Cyclophostin compounds (CyC).
Methods: Herein, we exploited this feature to evaluate the in vitro activity of CLR and AZM in combination with different CyC via the checkerboard assay on macrolide-susceptible and induced macrolide-resistant M. abscessus strains selected in vitro following exposure CLR and AZM.
Results: Our results emphasize the use of the CyC to prevent/overcome Erm(41)‑induced resistance and to restore macrolide susceptibility.
Conclusion: This work should expand our therapeutic arsenal in the fight against a antibioticresistant mycobacterial species and could provide the opportunity to revisit the therapeutic regimen for combating M. abscessus pulmonary infections in patients, and particularly in erm(41)-positive strains.
Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication and references: Not applicable. Competing interests: The authors declare that they have no competing interests. Not applicable.
(© 2024. The Author(s).)
Databáze: MEDLINE
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