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    High-level telithromycin resistance in laboratory-generated mutants of Streptococcus pneumoniae


    Walsh, Fiona and Willcock, Joanne and Amyes, Sebastian G.B. (2003) High-level telithromycin resistance in laboratory-generated mutants of Streptococcus pneumoniae. Journal of Antimicrobial Chemotherapy, 52 (3). pp. 345-353. ISSN 0305-7453

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    Abstract

    Resistance to macrolides in Streptococcus pneumoniae is usually mediated by methylation of 23S ribosomal RNA, encoded by the erm(B) methylation gene, or by efflux mediated by the mef(A) gene. Changes in the L4 and L22 ribosomal proteins have also been associated with macrolide resistance and reduced telithromycin activity. This study generated in vitro mutants from three parent strains of S. pneumoniae: 02J1175 [mef(A) +], 02J1095 [erm(B) +] and NCTC 13593 (macrolide susceptible). The erm(B) and the erm(B) upstream region, the mef(A) genes and the mef(A) upstream and downstream regions, the 23S rRNA genes encoding domains II and V and the L4 and L22 genes of the telithromycin-resistant strains were all amplified by PCR and all, except the mef(A) upstream and downstream regions, were sequenced. No changes were present in any of the genes of the mef(A) + mutants. No changes were found in the erm(B) genes, the 23S rRNA genes or the L4 protein genes of the erm(B) + mutants. However, a Lys-94 to Gln-94 amino acid mutation did occur in a mutant derived from erm(B) + with a telithromycin MIC of >32 mg/L. A 210 base pair deletion in the erm(B) upstream region was also present in this strain. We believe this is the first incidence of a Lys-94 to Gln-94 change in L22 associated with telithromycin resistance and also the first time that such a large deletion in the erm(B) upstream region has been identified in S. pneumoniae.

    Item Type: Article
    Keywords: telithromycin; Streptococcus pneumoniae; resistance;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 7484
    Identification Number: https://doi.org/10.1093/jac/dkg348
    Depositing User: Fiona Walsh
    Date Deposited: 04 Oct 2016 14:45
    Journal or Publication Title: Journal of Antimicrobial Chemotherapy
    Publisher: Oxford University Press
    Refereed: Yes
    URI:

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