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N. Wolter, A. M. Smith, D. J. Farrell, J. B. Northwood, S. Douthwaite and K. P. Klugman, “Telithromycin Resistance in Streptococcus Pneumoniae is Conferred by a Deletion in the Leader Sequence of erm(B) that Increases rRNA Methylation,” Antimicrobial Agents in Chemotherapy, Vol. 52, No. 2, 2008, pp. 435-440. doi:10.1128/AAC.01074-07

has been cited by the following article:

• TITLE: Effects of Clarithromycin at Sub-Minimum Inhibitory Concentrations on Early ermB Gene Expression, Metabolic Activity and Growth of an erm(B)-Expressing Macrolide-Resistant Strain of Streptococcus pneumoniae

  AUTHORS: Riana Cockeran, H. C. Steel, N. Wolter, L. de Gouveia, A. von Gottberg, K. P. Klugman, A. T. Leanord, D. J. Inverarity, T. J. Mitchell, C. Feldman, R. Anderson

  KEYWORDS: Clarithromycin; Macrolide-Resistance; Pneumococcus

  JOURNAL NAME: Open Journal of Respiratory Diseases, Vol.2 No.1, February 29, 2012

  ABSTRACT: Aim: To investigate the effects of exposure of a macrolide-resistant [erm (B)-expressing] strain of Streptococcus pneumoniae (strain 2507) to clarithromycin (0.5 and 5 mg/L) added at the outset and 6 hours after initiation of culture on early gene expression, energy metabolism, and growth. Methods: Bacterial growth was determined by turbidometric and colony counting procedures, energy metabolism by measurement of ATP, while analysis of gene expression was performed using reverse transcription-PCR and sequencing. Results: Addition of clarithromycin, at either concentration, at the outset of culture, caused transient suppression of growth of 10 - 12 hours duration, while delayed addition of antibiotic (during the logarithmic phase) resulted in an abrupt halt in growth followed by recovery. These inhibitory effects of clarithromycin on bacterial growth were associated with up-regulation of expression of erm(B), decreased ATP and protein synthesis, and were unaffected by inclusion of either catalase (500 and 1000 kunits/L), or competence-stimulating peptide (CSP-1, 0.5 mg/L). The inhibitory effects could, however, be overcome by pre-exposure of the bacteria to the antibiotic. Moreover, clarithromycin appeared to potentiate the antimicrobial actions of ceftriaxone, at sub-MIC concentrations, for strain 2507. Conclusions: Unlike several other common bacterial pathogens, the full expression of erm(B)-mediated macrolide resistance by the pneumococcus has a slow onset, which is associated with transient susceptibility to macrolides and inhibition of growth.