Open AccessEffect of katG Mutations on the Virulence of Mycobacterium tuberculosis and the Implication for Transmission in Humans
Author(s) -
Alexander S. Pym,
Brigitte SaintJoanis,
Stewart T. Cole
Publication year - 2002
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.70.9.4955-4960.2002
Subject(s) - mycobacterium tuberculosis , virulence , biology , isoniazid , tuberculosis , mutation , mutant , microbiology and biotechnology , multiple drug resistance , drug resistance , virology , inha , transmission (telecommunications) , gene , genetics , medicine , electrical engineering , pathology , engineering
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.