Journal Article

Effects of clofazimine on potassium uptake by a Trk-deletion mutant of <i>Mycobacterium tuberculosis</i>

M. C. Cholo, H. I. Boshoff, H. C. Steel, R. Cockeran, N. M. Matlola, K. J. Downing, V. Mizrahi and R. Anderson

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 57, issue 1, pages 79-84
Published in print January 2006 | ISSN: 0305-7453
Published online November 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki409
Effects of clofazimine on potassium uptake by a Trk-deletion mutant of Mycobacterium tuberculosis

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Objectives: This study was designed to investigate the effects of the membrane-active, anti-mycobacterial agent, clofazimine, on potassium (K+)-uptake by a mutant of Mycobacterium tuberculosis (MTB), in which the Trk system, the major K+ transporter of this microbial pathogen, had been selectively inactivated.

Methods: The ceoB and ceoC genes of MTB, which encode the TrkA proteins, CeoB and CeoC, were deleted by homologous recombination, and the double-knockout mutant and wild-type strains compared with respect to K+ uptake and growth in the presence and absence of clofazimine (0.015–2.5 mg/L) using radioassay procedures.

Results: Surprisingly, the magnitudes of K+ uptake and rate of growth of the ceoBC-knockout mutant were significantly (P < 0.05) greater than those of the wild-type strain, due, presumably, to induction of a back-up transporter. Exposure of both the wild-type strain and ceoBC-knockout mutant of MTB to clofazimine was accompanied by dose-related decreases in K+ uptake, as well as growth, which were of comparable magnitude for both strains.

Conclusions: These observations demonstrate that the major K+ transporter of MTB, Trk, as well as an uncharacterized inducible back-up system, is equally sensitive to the inhibitory actions of clofazimine.

Keywords: ceoB and ceoC genes; growth rate; uptake of rubidium

Journal Article.  3589 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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