Studies of the Novel Ketolide ABT-773: Transport, Binding to Ribosomes, and Inhibition of Protein Synthesis in Streptococcus pneumoniae

作者：John O. Capobianco, Zhensheng Cao, Virginia D. Shortridge, Zhenkun Ma, Robert K. Flamm, Ping Zhong · 发表于：Antimicrobial Agents and Chemotherapy · 年份：2000 · DOI：10.1128/aac.44.6.1562-1567.2000 · 被引用次数：84 · 研究领域：Pneumonia and Respiratory Infections、Pneumocystis jirovecii pneumonia detection and treatment、Antibiotic Resistance in Bacteria

Macrolide resistance in Streptococcus pneumoniae has been associated with two main mechanisms: target modification by Erm methyltransferases and efflux by macrolide pumps. The ketolide ABT-773, which has a 3-keto group and no L-cladinose sugar, represents a new class of drugs with in vitro activity against a variety of resistant bacteria. Several approaches were undertaken to understand how ABT-773 was able to defeat resistance mechanisms. We demonstrated tighter ribosome binding of ABT-773 than erythromycin. We also showed that ABT-773 (i) accumulated in macrolide-sensitive S. pneumoniae at a higher rate than erythromycin, (ii) was able to bind with methylated ribosomes, though at lower affinities than with wild-type ribosomes, and (iii) accumulated in S. pneumoniae strains with the efflux-resistant phenotype.