Mutational analysis of reduced telithromycin susceptibility of Streptococcus pneumoniae isolated clinically in Japan
Akiko Takaya
Department of Microbiology and Molecular Genetics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan
Search for more papers by this authorNaomi Kitagawa
Department of Microbiology and Molecular Genetics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan
Search for more papers by this authorYukano Kuroe
Department of Microbiology and Molecular Genetics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan
Search for more papers by this authorMitsuhiro Okazaki
Department of Clinical Laboratory, Kyorin University Hospital, Mitaka, Japan
Search for more papers by this authorEiji Yokoyama
Division of Bacteriology, Chiba Prefectural Institute of Public Health, Chiba, Japan
Search for more papers by this authorAkihito Wada
Department of Bacteriology, National Institute of Infectious Diseases, Tokyo, Japan
Search for more papers by this authorTomoko Yamamoto
Department of Microbiology and Molecular Genetics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan
Search for more papers by this authorAkiko Takaya
Department of Microbiology and Molecular Genetics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan
Search for more papers by this authorNaomi Kitagawa
Department of Microbiology and Molecular Genetics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan
Search for more papers by this authorYukano Kuroe
Department of Microbiology and Molecular Genetics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan
Search for more papers by this authorMitsuhiro Okazaki
Department of Clinical Laboratory, Kyorin University Hospital, Mitaka, Japan
Search for more papers by this authorEiji Yokoyama
Division of Bacteriology, Chiba Prefectural Institute of Public Health, Chiba, Japan
Search for more papers by this authorAkihito Wada
Department of Bacteriology, National Institute of Infectious Diseases, Tokyo, Japan
Search for more papers by this authorTomoko Yamamoto
Department of Microbiology and Molecular Genetics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan
Search for more papers by this authorEditor: Mark Enright
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 μg 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, ≥4 μg mL−1). Eight of these isolates (MIC 0.5–1 μg 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 μg mL−1) in S. pneumoniae may be caused by acquisition of the mefE-mel element only and additionally conferred by the ermB determinant.
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