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Infection and Immunity, September 2002, p. 4955-4960, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.4955-4960.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Effect of katG Mutations on the Virulence of Mycobacterium tuberculosis and the Implication for Transmission in Humans

Alexander S. Pym,1,2 Brigitte Saint-Joanis,1 and Stewart T. Cole1*

Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, Paris, France,1 Liverpool School of Tropical Medicine, Liverpool, United Kingdom2

Received 5 December 2001/ Returned for modification 12 February 2002/ Accepted 12 June 2002

The usefulness of isoniazid (INH), a key component of short-course chemotherapy of tuberculosis, is threatened by the emergence of drug-resistant strains of Mycobacterium tuberculosis with mutations in the katG gene. It is shown here that the most commonly occurring KatG mutation, where Ser 315 is replaced by Thr (S315T), is associated with clinically significant levels of INH resistance. In contrast to another resistant isolate, in which Pro replaces Thr 275, the S315T mutant produces active catalase-peroxidase and is virulent in the mouse model of the disease, indicating that a significant loss of bacterial fitness does not result from this frequent mutation. The implications of this finding for the transmission and reactivation of multidrug-resistant strains of M. tuberculosis are severe.

* Corresponding author. Mailing address: Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris Cedex, France. Phone: 33-1-45688446. Fax: 33-1-40613583. E-mail: stcole{at}pasteur.fr.

Editor: S. H. E. Kaufmann

Infection and Immunity, September 2002, p. 4955-4960, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.4955-4960.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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