Sarecycline inhibits protein translation in Cutibacterium acnes 70S ribosome using a two-site mechanism.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
11 04 2023
11 04 2023
Historique:
accepted:
07
02
2023
revised:
01
02
2023
received:
12
10
2022
medline:
12
4
2023
pubmed:
4
3
2023
entrez:
3
3
2023
Statut:
ppublish
Résumé
Acne vulgaris is a chronic disfiguring skin disease affecting ∼1 billion people worldwide, often having persistent negative effects on physical and mental health. The Gram-positive anaerobe, Cutibacterium acnes is implicated in acne pathogenesis and is, therefore, a main target for antibiotic-based acne therapy. We determined a 2.8-Å resolution structure of the 70S ribosome of Cutibacterium acnes by cryogenic electron microscopy and discovered that sarecycline, a narrow-spectrum antibiotic against Cutibacterium acnes, may inhibit two active sites of this bacterium's ribosome in contrast to the one site detected previously on the model ribosome of Thermus thermophilus. Apart from the canonical binding site at the mRNA decoding center, the second binding site for sarecycline exists at the nascent peptide exit tunnel, reminiscent of the macrolides class of antibiotics. The structure also revealed Cutibacterium acnes-specific features of the ribosomal RNA and proteins. Unlike the ribosome of the Gram-negative bacterium Escherichia coli, Cutibacterium acnes ribosome has two additional proteins, bS22 and bL37, which are also present in the ribosomes of Mycobacterium smegmatis and Mycobacterium tuberculosis. We show that bS22 and bL37 have antimicrobial properties and may be involved in maintaining the healthy homeostasis of the human skin microbiome.
Identifiants
pubmed: 36864821
pii: 7067950
doi: 10.1093/nar/gkad103
pmc: PMC10085706
doi:
Substances chimiques
Anti-Bacterial Agents
0
sarecycline
94O110CX2E
Tetracyclines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2915-2930Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.
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