Document Detail

Telithromycin resistance in Streptococcus pneumoniae is conferred by a deletion in the leader sequence of erm(B) that increases rRNA methylation.
MedLine Citation:
PMID:  18056269     Owner:  NLM     Status:  MEDLINE    
A telithromycin-resistant clinical isolate of Streptococcus pneumoniae (strain P1501016) has been found to contain a version of erm(B) that is altered by a 136-bp deletion in the leader sequence. By allele replacement mutagenesis, a second strain of S. pneumoniae (PC13) with a wild-type erm(B) gene was transformed to the telithromycin-resistant phenotype by introduction of the mutant erm(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 microg/ml), the transformed PC13 strain is constitutively resistant (MIC of 16 mug/ml). Expression of erm(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 mutant erm(B) gene that is expressed at a constitutively higher level than the inducible wild-type gene. Elevated erm(B) expression results in a higher level of rRNA methylation that presumably hinders telithromycin binding to the ribosome.
Nicole Wolter; Anthony M Smith; David J Farrell; John Blackman Northwood; Stephen Douthwaite; Keith P Klugman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-12-03
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  52     ISSN:  0066-4804     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-01-24     Completed Date:  2008-04-29     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  435-40     Citation Subset:  IM    
Respiratory and Meningeal Pathogens Research Unit, National Institute for Communicable Diseases, Private Bag X4, Sandringham 2131, South Africa.
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MeSH Terms
5' Untranslated Regions / chemistry,  genetics*
Amino Acid Sequence
Anti-Bacterial Agents / pharmacology*
Drug Resistance, Bacterial
Ketolides / pharmacology*
Methyltransferases / chemistry,  genetics*
Microbial Sensitivity Tests
Molecular Sequence Data
RNA, Ribosomal / metabolism*
Sequence Deletion*
Streptococcus pneumoniae / drug effects*,  genetics,  growth & development
Reg. No./Substance:
0/5' Untranslated Regions; 0/Anti-Bacterial Agents; 0/Ketolides; 0/RNA, Ribosomal; 0/telithromycin; EC 2.1.1.-/Methyltransferases; EC (adenosine-O-2'-)methyltransferase

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