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Antimicrobial Agents and Chemotherapy, August 1999, p. 1866-1869, Vol. 43, No. 8
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Physiological Cost of Rifampin Resistance Induced In Vitro in Mycobacterium tuberculosis

O. J. Billington, T. D. McHugh, and S. H. Gillespie*

Department of Medical Microbiology, Royal Free and University College Medical School, Royal Free Campus, London NW3 2PF, United Kingdom

Received 8 February 1999/Returned for modification 29 March 1999/Accepted 11 May 1999

Drug-resistant Mycobacterium tuberculosis is a major threat to public health. In clinical practice, a limited number of resistance mutations in a short sequence of the beta subunit of RNA polymerase (encoded by rpoB) have been described. Spontaneous resistance to rifampin was induced in vitro in M. tuberculosis H37Rv (ATCC 9360). Only three resistance patterns could be detected by PCR-single-strand conformation polymorphism analysis. Sequence analysis revealed that Ser531right-arrowLeu arose most frequently, followed by His526right-arrowArg and then either His526right-arrowTyr or His526right-arrowAsp. The relative Darwinian fitness of all but one of the mutant genotypes was less than that of the susceptible parent and, for these mutations, there was a significant correlation between fitness and clinical isolation rate (regression analysis P = 0.026). The fitness deficit in some mutants was small, suggesting that there is little likelihood of a spontaneous reversion to susceptibility.

* Corresponding author. Mailing address: Department of Medical Microbiology, Royal Free and University College Medical School, Royal Free Campus, Rowland Hill St., London NW3 2PF, United Kingdom. Phone: 44-0-171-794-0500. Fax: 44-0-171-794-0433. E-mail: stepheng{at}rfhsm.ac.uk.

Antimicrobial Agents and Chemotherapy, August 1999, p. 1866-1869, Vol. 43, No. 8
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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