Open AccessTelithromycin Resistance in Streptococcus pneumoniae Is Conferred by a Deletion in the Leader Sequence of erm (B) That Increases rRNA Methylation
Author(s) -
Nicole Wolter,
Anthony M. Smith,
David J. Farrell,
John Blackman Northwood,
Stephen Douthwaite,
Keith P. Klugman
Publication year - 2008
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.01074-07
Subject(s) - telithromycin , microbiology and biotechnology , biology , ketolide , streptococcus pneumoniae , erythromycin , mutant , methylation , gene , antibiotics , genetics
A telithromycin-resistant clinical isolate ofStreptococcus pneumoniae (strain P1501016) has been found to contain a version oferm (B) that is altered by a 136-bp deletion in the leader sequence. By allele replacement mutagenesis, a second strain ofS. pneumoniae (PC13) with a wild-typeerm (B) gene was transformed to the telithromycin-resistant phenotype by introduction of the mutanterm (B) gene. Whereas the wild-type PC13 strain showed slight telithromycin resistance only after induction by erythromycin (telithromycin MIC increased from 0.06 to 0.5 μg/ml), the transformed PC13 strain is constitutively resistant (MIC of 16 μg/ml). Expression oferm (B) was quantified by real-time reverse transcription-PCR in the presence of erythromycin or telithromycin;erm (B) expression was significantly higher in the transformed PC13 strain than the wild-type strain. Furthermore, the transformed strain had significantly higher levels of ribosomal methylation in the absence as well as in the presence of the antibiotics. Growth studies showed that the transformed PC13 strain had a shorter lag phase than the wild-type strain in the presence of erythromycin. Telithromycin resistance is conclusively shown to be conferred by the mutanterm (B) gene that is expressed at a constitutively higher level than the inducible wild-type gene. Elevatederm (B) expression results in a higher level of rRNA methylation that presumably hinders telithromycin binding to the ribosome.