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TitleMechanistic Basis for the Translation Inhibition of Cutibacterium acnes by Clindamycin.
Journal, issue, pagesJ Invest Dermatol, Vol. 144, Issue 11, Page 2553-22561.e3, Year 2024
Publish dateAug 8, 2024
AuthorsIvan B Lomakin / Swapnil C Devarkar / Ayman Grada / Christopher G Bunick /
PubMed AbstractInflammation and the Gram-positive anaerobic bacterium Cutibacterium acnes, which is implicated in acne pathogenesis and pilosebaceous-unit inflammation, are the main targets of antibiotic-based ...Inflammation and the Gram-positive anaerobic bacterium Cutibacterium acnes, which is implicated in acne pathogenesis and pilosebaceous-unit inflammation, are the main targets of antibiotic-based therapy against acne vulgaris (acne). The most widely used antibiotics in acne therapy are tetracyclines, macrolides, and lincosamides. Unfortunately, C. acnes bacteria over the past several decades have demonstrated increased resistance to these antibiotics, particularly to clindamycin. The precise knowledge of how antibiotics interact with their clinical target is needed to overcome this problem. Toward this goal, we determined the structure of clindamycin in complex with the ribosome of C. acnes at 2.53 Å resolution using cryogenic electron microscopy. The galactose sugar moiety of clindamycin interacts with nucleotides of the 23S ribosomal RNA directly or through a conserved network of water-mediated interactions. Its propyl pyrrolidinyl group interacts with the 23S ribosomal RNA through van der Waals forces. Clindamycin binding to the C. acnes ribosome interferes with both: proper orientation of the aminoacyl group of the A-site bound transfer RNA that is needed for peptide bond formation and with the extension of the nascent peptide. Our data are important for advancing the understanding of antibiotic resistance and development of narrow-spectrum antibacterial drugs, which is an urgent need for contemporary antibiotic stewardship.
External linksJ Invest Dermatol / PubMed:39122144
MethodsEM (single particle)
Resolution2.53 Å
Structure data

45185

9c4g

EMDB-45185, PDB-9c4g:
Cutibacterium acnes 50S ribosomal subunit with Clindamycin bound
Method: EM (single particle) / Resolution: 2.53 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-CLY:
CLINDAMYCIN / medication, antibiotic*YM

ChemComp-HOH:
WATER

Source
  • cutibacterium acnes (bacteria)
KeywordsANTIBIOTIC / ribosome / clindamycin / acne

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