scholarly journals Isoniazid-resistance conferring mutations in Mycobacterium tuberculosis KatG: Catalase, peroxidase, and INH-NADH adduct formation activities

2010 ◽  
Vol 19 (3) ◽  
pp. 458-474 ◽  
Author(s):  
Christine E. Cade ◽  
Adrienne C. Dlouhy ◽  
Katalin F. Medzihradszky ◽  
Saida Patricia Salas-Castillo ◽  
Reza A. Ghiladi
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Adduct Formation ◽  
Isoniazid Resistance ◽  
Catalase Peroxidase

Significance of catalase-peroxidase (KatG) mutations in mediating isoniazid resistance in clinical strains of Mycobacterium tuberculosis

2018 ◽  
Vol 15 ◽  
pp. 111-120 ◽  
Author(s):  
Ameeruddin Nusrath Unissa ◽  
George Priya Doss C ◽  
Thirumal Kumar ◽  
Swathi Sukumar ◽  
Appisetty Ramya Lakshmi ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Isoniazid Resistance ◽  
Clinical Strains ◽  
Catalase Peroxidase

Analysis of interactions of clinical mutants of catalase-peroxidase (KatG) responsible for isoniazid resistance in Mycobacterium tuberculosis with derivatives of isoniazid

2017 ◽  
Vol 11 ◽  
pp. 57-67 ◽  
Author(s):  
Ameeruddin Nusrath Unissa ◽  
George Priya Doss C. ◽  
Thirumal Kumar ◽  
Sukumar Swathi ◽  
Appisetty Ramya Lakshmi ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Isoniazid Resistance ◽  
Catalase Peroxidase ◽  
Derivatives Of

scholarly journals The catalase—peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis

Nature ◽  
1992 ◽  
Vol 358 (6387) ◽  
pp. 591-593 ◽  
Author(s):  
Ying Zhang ◽  
Beate Heym ◽  
Bryan Allen ◽  
Douglas Young ◽  
Stewart Cole
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Isoniazid Resistance ◽  
Peroxidase Gene ◽  
Catalase Peroxidase

scholarly journals Isoniazid Activation Defects in Recombinant Mycobacterium tuberculosis Catalase-Peroxidase (KatG) Mutants Evident in InhA Inhibitor Production

2003 ◽  
Vol 47 (2) ◽  
pp. 670-675 ◽  
Author(s):  
Chih-Jen Wei ◽  
Benfang Lei ◽  
James M. Musser ◽  
Shiao-Chun Tu
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Amino Acid Replacement ◽  
Site Directed Mutagenesis ◽  
Wild Type ◽  
Isoniazid Resistance ◽  
Enoyl Reductase ◽  
Mutant Proteins ◽  
Catalase Peroxidase ◽  
Free Radical Formation ◽  
Inha Inhibitor

ABSTRACT Mycobacterium tuberculosis KatG catalyzes the activation of the antitubercular agent isoniazid to yield an inhibitor targeting enoyl reductase (InhA). However, no firm biochemical link between many KatG variants and isoniazid resistance has been established. In the present study, six distinct KatG variants identified in clinical Mycobacterium tuberculosis isolates resistant to isoniazid were generated by site-directed mutagenesis, and the recombinant mutant proteins (KatGA110V, KatGA139P, KatGS315N, KatGL619P, KatGL634F, and KatGD735A) were purified and characterized with respect to their catalase-peroxidase activities (in terms of k cat/Km ), rates of free-radical formation from isoniazid oxidation, and, moreover, abilities to activate isoniazid. The A110V amino acid replacement did not result in significant alteration of KatG activities except that the peroxidase activity was enhanced. The other mutations, however, resulted in modestly reduced catalase and peroxidase catalytic efficiencies and, for the four mutants tested, significantly lower activities to oxidize isoniazid. Compared to the wild-type enzyme, the ability of the KatGL634F, KatGA139P, and KatGD735A variants to activate isoniazid decreased by 36%, 76%, and 73%, respectively, whereas the KatGS315N and KatGL619P variants completely lost their abilities to convert isoniazid into the InhA inhibitor. In addition, the inclusion of exogenous Mn2+ to the isoniazid activation reaction mix significantly improved the ability of wild-type and KatG mutants to produce the InhA inhibitor.

scholarly journals Using cryo-EM to understand antimycobacterial resistance in the catalase-peroxidase (KatG) from Mycobacterium tuberculosis

Structure ◽  
2021 ◽  
Author(s):  
Asma Munir ◽  
Michael T. Wilson ◽  
Steven W. Hardwick ◽  
Dimitri Y. Chirgadze ◽  
Jonathan A.R. Worrall ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Catalase Peroxidase
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