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Proteomics ; 24(10): e2300332, 2024 May.
Article in English | MEDLINE | ID: mdl-38238893

ABSTRACT

Nontuberculous Mycobacteria (NTM) are a group of emerging bacterial pathogens that have been identified in cystic fibrosis (CF) patients with microbial lung infections. The treatment of NTM infection in CF patients is challenging due to the natural resistance of NTM species to many antibiotics. Mycobacterium abscessus is one of the most common NTM species found in the airways of CF patients. In this study, we characterized the extracellular vesicles (EVs) released by drug-sensitive M. abscessus untreated or treated with clarithromycin (CLR), one of the frontline anti-NTM drugs. Our data show that exposure to CLR increases mycobacterial protein trafficking into EVs as well as the secretion of EVs in culture. Additionally, EVs released by CLR-treated M. abscessus increase M. abscessus resistance to CLR when compared to EVs from untreated M. abscessus. Proteomic analysis further indicates that EVs released by CLR-treated M. abscessus carry an increased level of 50S ribosomal subunits, the target of CLR. Taken together, our results suggest that EVs play an important role in M. abscessus resistance to CLR treatment.


Subject(s)
Anti-Bacterial Agents , Clarithromycin , Drug Resistance, Bacterial , Extracellular Vesicles , Mycobacterium Infections, Nontuberculous , Mycobacterium abscessus , Extracellular Vesicles/metabolism , Extracellular Vesicles/drug effects , Mycobacterium abscessus/drug effects , Mycobacterium abscessus/metabolism , Clarithromycin/pharmacology , Drug Resistance, Bacterial/drug effects , Humans , Anti-Bacterial Agents/pharmacology , Mycobacterium Infections, Nontuberculous/microbiology , Proteomics/methods , Bacterial Proteins/metabolism
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