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

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.

DOI: 10.4236/ojrd.2012.22009                

Abstract

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 < 0.05) at concentrations of 0.4 and 0.1 mg/L respectively. Conclusions: These observations are compatible with the mycobacterial membrane as being the putative site of action of 7-MJ, targeting microbial energy metabolism and K⁺ transport.

Keywords

Adenosine Triphosphate; Cell Membrane; Energy Metabolism; Potassium

Conflicts of Interest

The authors declare no conflicts of interest.

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