1041 Atomic resolution structure of the cutibacterium acnes ribosome reveals the mechanism of protein synthesis inhibition by the antibiotic sarecycline

Antibiotic resistance is a global problem. Acne vulgaris chronic disfiguring skin disease affecting ∼1 billion people worldwide, often having persistent negative effects on physical and mental health. Prolonged treatment of acne with broad-spectrum antibiotics results in antibiotic at concerning rates the Gram-positive anaerobe Cutibacterium acnes, commensal implicated pathogenesis. We determined 2.8-Å resolution structure 70S ribosome acnes by cryogenic electron microscopy discovered that sarecycline, narrow-spectrum against may inhibit two active sites this bacterium’s contrast to one site detected previously model Thermus thermophilus. Apart from canonical binding mRNA decoding center, second for sarecycline exists nascent peptide exit tunnel, reminiscent macrolides class antibiotics. The also revealed acnes-specific features ribosomal RNA proteins. Six proteins bound Zn2+, providing molecular rationale zinc supplementation therapy. Unlike Gram-negative bacterium Escherichia coli, has additional proteins, which are present ribosomes Mycobacterium smegmatis tuberculosis. show these have antimicrobial properties be involved maintaining healthy homeostasis human microbiome.