title: Mutational analysis of reduced telithromycin susceptibility of Streptococcus pneumoniae isolated clinically in Japan.
abstract: A total of 132 Streptococcus pneumoniae isolates collected between 2005 and 2006 in Japan were examined for susceptibility to telithromycin (TEL) and macrolide. The overall resistance to macrolide was 80%. Among the isolates, 128 strains had low-level TEL susceptibility (minimal inhibitory concentrations [MICs] 0.03-1 microg mL(-1)), suggesting that pneumococci with reduced susceptibility to TEL have appeared without prior exposure to the drug, although none of the isolates were assigned as TEL-resistant (breakpoint, > or = 4 microg mL(-1)). Eight of these isolates (MIC 0.5-1 microg mL(-1)) were analyzed for macrolide resistance determinants and genetic relatedness. They all carried mefE-mel, which encodes the macrolide efflux genetic assembly, and three also harbored ermB, which encodes rRNA methylase. Allele replacement mutagenesis of the corresponding genes in the clinical isolates revealed that reduced TEL susceptibility (MIC 1 microg mL(-1)) in S. pneumoniae may be caused by acquisition of the mefE-mel element only and additionally conferred by the ermB determinant.
authors.affiliation: Department of Microbiology and Molecular Genetics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Takaya
authors.forename: Naomi
authors.initials: N
authors.lastname: Kitagawa
authors.forename: Yukano
authors.initials: Y
authors.lastname: Kuroe
authors.forename: Kikutarou
authors.initials: K
authors.lastname: Endo
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Okazaki
authors.forename: Eiji
authors.initials: E
authors.lastname: Yokoyama
authors.forename: Akihito
authors.initials: A
authors.lastname: Wada
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016172:DNA Fingerprinting; D004252:DNA Mutational Analysis; D024881:Drug Resistance, Bacterial; D016521:Electrophoresis, Gel, Pulsed-Field; D005798:Genes, Bacterial; D005838:Genotype; D007564:Japan; D048628:Ketolides / Q000494:pharmacology*; D018942:Macrolides / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D011008:Pneumococcal Infections / Q000382:microbiology*; D011995:Recombination, Genetic; D013296:Streptococcus pneumoniae / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D014169:Transformation, Bacterial
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; C106791:telithromycin