DVirulence in isoniazid-resistant clinical isolates of Mycobacterium tuberculosis from south India .

Unissa, A.N.; Narayanan, S.; Selvakumar, N.

International Journal of Molecular an d Clinical Microbiology; 2011; 1; 87-96.      

Abstract: Isoniazid, is the only antituberculous drug for which the relation between lack of virulence and acquisition of resistance was associated. INH-resistant mutants were shown to contain defective katG gene. Classical studies showed that INH-resistant south Indian isolates have lower virulence in guinea pigs and higher susceptibility to H 2 O 2 . It is of interest to assess the virulence in south Indian clinical mutants of KatG (catalase-peroxidase enzyme) associated with INH resistance. Five INH-resistant clinical isolates were selected on the basis of mutation in kat G gene. Mutant isolates were used for infecting macrophage cell line (THP-1) and for the assessment of enzyme activity. In comparison to control H37Rv, Ser315Thr mutant exhibits similar virulence and reduction (4% and 17%) in catalase (C) and peroxidase (P) activity. For the mutants, Ser315Iso and Ser315Arg, the virulent nature was slightly reduced with 3% and 2%, and significant reduction was observed in the C (50%; 47%) and P (36%; 43%) activity respectively. Ser315Asn indicates 4% reduction in virulence with significant reduction in C (56%) and P (64%) activity. Asn138Ser mutant displayed low-level virulence, CP activity showed 47% and 56% reduction. The results indicate that similar level of virulence in all the mutants except Asn138Ser which showed relatively low-level whereas a significant decrease in C and P activity was observed in all mutants except Ser315Thr. The study suggests despite the fact that all mutants do not compromise survival or virulence yet provides INH resistance.

Keywords: Mycobacterium tuberculosis; virulence; INH resistance; KatG mutants

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