PXD055560

PXD055560 is an original dataset announced via ProteomeXchange.

Title	Cyclophostin and Cyclipostins analogues counteract macrolide-induced resistance mediated by Erm(41) in Mycobacterium abscessus
Description	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, including clarithromycin (CLR) and azithromycin (AZM), represent the current cornerstone of antibiotherapy against M. abscessus complex. However, prolonged exposure to macrolides can induce the apparition of Erm(41)-mediated resistance, limiting their spectrum of activity and often leading to therapeutic failure. Therefore, inhibiting Erm(41) could thwart this resistance mechanism to maintain macrolide susceptibility and avoid the therapeutic failure. In a previous study, the Erm(41) methyltransferase was identified as a target enzyme of Cyclipostins and Cyclophostin compounds (CyC). Herein, we took advantage of this feature to evaluate the in vitro activity of clarithromycin and azithromycin in combination with different CyC via the checkerboard assay on macrolide susceptible and induced macrolide-resistant M. abscessus generated by either clarithromycin or azithromycin exposure. Our results emphasize the use of the CyC to prevent/overcome Erm(41) induced resistance, restore macrolide susceptibility. This work should help to expand our therapeutic arsenal in the fight against a particularly antibiotic resistant mycobacterial species and could provide the opportunity to revisit the therapeutic regimen for combating M. abscessus pulmonary infections in CF patients, and particularly in erm(41)-positive strains.
HostingRepository	PRIDE
AnnounceDate	2024-12-05
AnnouncementXML	Submission_2024-12-05_07:35:22.844.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	AUDEBERT Stephane
SpeciesList	scientific name: Bacteria; NCBI TaxID: NCBITaxon:2; scientific name: Mycobacterium abscessus; NCBI TaxID: 36809;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-04 12:16:45	ID requested
⏵ 1	2024-12-05 07:35:24	announced

Sarrazin M, Poncin I, Fourquet P, Audebert S, Camoin L, Denis Y, Santucci P, Spilling CD, Kremer L, Le Moigne V, Herrmann JL, Cavalier JF, Canaan S, Cyclophostin and Cyclipostins analogues counteract macrolide-induced resistance mediated by erm(41) in Mycobacterium abscessus. J Biomed Sci, 31(1):103(2024) [pubmed]

10.1186/s12929-024-01091-w;

submitter keyword: LC-MSMS, resistance, macrolide, synergy testing, Erm(41), drug susceptibility,Mycobacterium abscessus

Dr. CANAAN Stephane
contact affiliation	LISM – CNRS UMR7255 31 Chemin Joseph Aiguier 13402 Marseille cedex 20 France
contact email	canaan@imm.cnrs.fr
lab head
AUDEBERT Stephane
contact affiliation	Marseille Proteomic, Centre de Recherche en Cancérologie de Marseille, Inserm UMR1068, CNRS UMR7258, Aix Marseille Université U105, Institut Paoli Calmettes, 27 Boulevard Leï Roure CS30059 13273 Marseille Cedex 09 France
contact email	stephane.audebert@inserm.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055560
     1. Label: PRIDE project
     2. Name: Cyclophostin and Cyclipostins analogues counteract macrolide-induced resistance mediated by Erm(41) in Mycobacterium abscessus