Regulation of the macrolide resistance ABC-F translation factor MsrD.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
01 07 2023
01 07 2023
Historique:
received:
23
08
2022
accepted:
19
06
2023
medline:
3
7
2023
pubmed:
2
7
2023
entrez:
1
7
2023
Statut:
epublish
Résumé
Antibiotic resistance ABC-Fs (ARE ABC-Fs) are translation factors that provide resistance against clinically important ribosome-targeting antibiotics which are proliferating among pathogens. Here, we combine genetic and structural approaches to determine the regulation of streptococcal ARE ABC-F gene msrD in response to macrolide exposure. We show that binding of cladinose-containing macrolides to the ribosome prompts insertion of the leader peptide MsrDL into a crevice of the ribosomal exit tunnel, which is conserved throughout bacteria and eukaryotes. This leads to a local rearrangement of the 23 S rRNA that prevents peptide bond formation and accommodation of release factors. The stalled ribosome obstructs the formation of a Rho-independent terminator structure that prevents msrD transcriptional attenuation. Erythromycin induction of msrD expression via MsrDL, is suppressed by ectopic expression of mrsD, but not by mutants which do not provide antibiotic resistance, showing correlation between MsrD function in antibiotic resistance and its action on this stalled complex.
Identifiants
pubmed: 37393329
doi: 10.1038/s41467-023-39553-8
pii: 10.1038/s41467-023-39553-8
pmc: PMC10314930
doi:
Substances chimiques
Anti-Bacterial Agents
0
Macrolides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3891Informations de copyright
© 2023. The Author(s).
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