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Investigation of the Anti-Mycobacterial Mechanism of Action of 7-Methyljuglone

Open Journal of Respiratory Diseases 2012年第2期2卷 60-62页

作者： Veneesha Thaver J. J. M. Meyer riana cockeran Moloko C. Cholo Ronald Anderson Namrita Lall Department of Physiology University of Limpopo Medical University of South Africa Campus Pretoria South Africa Department of Plant Science Faculty of Natural and Agricultural Sciences University of Pretoria Pretoria South Africa MRC Unit for Inflammation and Immunity Department of Immunology Faculty of Health Sciences University of Pretoria and Tshwane Academic Division of the National Health Laboratory Service Pretoria South Africa

Objectives: Although the naphthoquinone, 7-methyljuglone (7-MJ), is active against Mycobacterium tuberculosis (MTB) in vitro, neither the cellular site nor mechanism of anti-mycobacterial action of this agent has been identified. The primary objective of the current study was to investigate the mycobacterial outer membrane as a potential target of 7-MJ by measuring the effects of this agent (0.023 - 1.5 mg/L) on microbial ATP levels and uptake of K+ . Methods: Bioluminescence and radiometric (uptake of 86Rb+) procedures were used to assay microbial ATP levels and K+ transport respectively. Results: Exposure of MTB (strain H37Rv) to 7-MJ for 60 min resulted in dose-related decreases in both microbial ATP levels and uptake of 86Rb+ which achieved statistical significance (P + transport.

关键词： Adenosine Triphosphate Cell Membrane Energy Metabolism Potassium

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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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Open Journal of Respiratory Diseases 2012年第1期2卷 1-8页

作者： 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 Division of Infection and Immunity Glasgow Biomedical Research Centre University of Glasgow Glasgow UK Division of Pulmonology Department of Internal Medicine Charlotte Maxeke Johannesburg Academic Hospital and University of the Witwatersrand Johannesburg South Africa Hubert Department of Global Health Rollins School of Public Health and Division of Infectious Diseases School of Medicine Emory University Atlanta USA Medical Research Council (MRC) Unit for Inflammation and Immunity Department of Immunology Faculty of Health Sciences University of Pretoria and Tshwane Academic Division of the National Health Laboratory Service Pretoria South Africa Microbiology Department Southern General Hospital Glasgow UK Respiratory and Meningeal Pathogens Research Unit National Institute for Communicable Diseases of the National Health Laboratory Service and Faculty of Health Sciences University of the Witwatersrand Johannesburg South Africa

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.

关键词： Clarithromycin Macrolide-Resistance Pneumococcus

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