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

• DOI: 10.1128/aac.44.6.1562-1567.2000
• Publication Date: 2002-07-27T09:56:57Z
• Authors: John O. Capobianco; ZhenSheng Cao; Virginia D. Short...; ZhenKun Ma; Robert K. Flamm; Ping Zhong
• Keywords: Ketolide; Efflux

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