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
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Authors
Cockeran, Riana
Wolter, Nicole
De Gouveia, L.
Von Gottberg, Anne
Klugman, Keith P.
Leanord, A.T.
Inverarity, D.J.
Mitchell, Timothy J.
Feldman, Charles
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Scientific Research Publishing Inc
Abstract
AIM: To investigate the effects of exposure of a macrolide-resistant [erm(B)-expressing] strain of Streptococcus pneumo- niae (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 per- formed 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 antibi-otic (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 compe- tence-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.
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Keywords
Clarithromycin, Pneumococcus, Macrolide-resistance
Sustainable Development Goals
Citation
Cockeran, R, Steel, HC, Wolter, N, De Gouveia, L, Von Gottberg, A, Klugman, KP, Leanord, AT, Inverarity, DJ, Mitchell, TJ, Feldman, C & Anderson, R 2012, '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', Open Journal of Respiratory Diseases, vol. 2, no. 1, pp. 1-8.