Mycobacterium smegmatis MfpC is a GEF that regulates mfpA translationally to alter the fluoroquinolone efficacy.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
23 Aug 2024
23 Aug 2024
Historique:
received:
30
01
2024
accepted:
14
08
2024
medline:
24
8
2024
pubmed:
24
8
2024
entrez:
23
8
2024
Statut:
epublish
Résumé
Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a serious threat to global public health. Fluoroquinolones (FQs) are effective against M. tuberculosis; however, resistant strains have limited their efficacy. Mycobacterium fluoroquinolone resistance protein A (MfpA) confers intrinsic resistance to FQs; however, its regulatory mechanisms remain largely unknown. Using M. smegmatis as a model, we investigated whether MfpC is necessary for FQ susceptibility. MfpC mutants were sensitive to moxifloxacin, indicating that MfpC is involved in FQ susceptibility. By testing the mfpC inactivation phenotype in different mutants and using mycobacterial protein fragment complementation, we demonstrated that the function of MfpC depends on its interactions with MfpB. Guanine nucleotide exchange assays and site-directed mutagenesis confirmed that MfpC acts as a guanine nucleotide exchange factor to regulate MfpB. We propose that MfpB influences MfpA at the translational level. In summary, we reveal the role of MfpC in regulating the function of MfpA in FQ resistance.
Identifiants
pubmed: 39179666
doi: 10.1038/s42003-024-06737-x
pii: 10.1038/s42003-024-06737-x
doi:
Substances chimiques
Fluoroquinolones
0
Bacterial Proteins
0
Guanine Nucleotide Exchange Factors
0
Anti-Bacterial Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1035Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82072246
Informations de copyright
© 2024. The Author(s).
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