ジャーナル: Life Sci Alliance / 年: 2025 タイトル: Structural studies on ribosomes of differentially macrolide-resistant strains. 著者: André Rivalta / Aliza Fedorenko / Alexandre Le Scornet / Sophie Thompson / Yehuda Halfon / Elinor Breiner Goldstein / Sude Çavdaroglu / Tal Melenitzky / Disha-Gajanan Hiregange / Ella ...著者: André Rivalta / Aliza Fedorenko / Alexandre Le Scornet / Sophie Thompson / Yehuda Halfon / Elinor Breiner Goldstein / Sude Çavdaroglu / Tal Melenitzky / Disha-Gajanan Hiregange / Ella Zimmerman / Anat Bashan / Mee-Ngan Frances Yap / Ada Yonath / 要旨: Antimicrobial resistance is a major global health challenge, diminishing the efficacy of many antibiotics, including macrolides. In , an opportunistic pathogen, macrolide resistance is primarily ...Antimicrobial resistance is a major global health challenge, diminishing the efficacy of many antibiotics, including macrolides. In , an opportunistic pathogen, macrolide resistance is primarily mediated by Erm-family methyltransferases, which mono- or dimethylate A2058 in the 23S ribosomal RNA, reducing drug binding. Although macrolide-ribosome interactions have been characterized in nonpathogenic species, their structural basis in clinically relevant pathogens remains limited. In this study, we investigate the impact of -mediated resistance on drug binding by analyzing ribosomes from strains with varying levels of expression and activity. Using cryo-electron microscopy, we determined the high-resolution structures of solithromycin-bound ribosomes, including those with dimethylated A2058. Our structural analysis reveals the specific interactions that enable solithromycin binding despite double methylation and resistance, as corroborated by microbiological and biochemical data, suggesting that further optimization of ketolide-ribosome interactions could enhance macrolide efficacy against resistant strains.
全体 : Cryo-EM structure of the ribosome of a MLSb sensitive S. aureus s...
全体
名称: Cryo-EM structure of the ribosome of a MLSb sensitive S. aureus strain "KES34" in complex with solithromycin
要素
複合体: Cryo-EM structure of the ribosome of a MLSb sensitive S. aureus strain "KES34" in complex with solithromycin
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超分子 #1: Cryo-EM structure of the ribosome of a MLSb sensitive S. aureus s...
超分子
名称: Cryo-EM structure of the ribosome of a MLSb sensitive S. aureus strain "KES34" in complex with solithromycin タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#28