Effect of rifampicin & isoniazid on cytochrome P-450 in mycobacteria.
OBJECTIVE
Rifampicin and isoniazid are the most important first line drugs used in the treatment of tuberculosis. These drugs are also used in combination with other medications to treat co-infections. It, therefore, becomes important to study the effect of these drugs on the drug metabolizing system, namely, cytochrome P-450, not only in the host but also in the bacteria. We report the effect of rifampicin and isoniazid on the cytochrome P-450 activity in Mycobacterium smegmatis and M. tuberculosis H37Rv.


METHODS
Subinhibitory concentrations of rifampicin and isoniazid were added to the organisms after they had attained the growth phase and cytochrome P-450 activity was estimated in the membranous fractions of the bacteria at different time points.


RESULTS
Rifampicin was able to significantly enhance cytochrome P-450 in both M. smegmatis and M. tuberculosis H37Rv. Isoniazid was found to inhibit cytochrome P-450 in M. tuberculosis H37Rv, while there seemed to be no effect in M. smegmatis.


CONCLUSIONS
We report here the effect of rifampicin and isoniazid on mycobacterial cytochrome P-450. These findings are similar to those found in eukaryotic organisms. The role of mycobacterial cytochrome P-450 in the metabolism of drugs within the bacteria needs to be elucidated.
Ramachandran
Geetha
G
Tuberculosis Research Centre (ICMR), Chennai, India.
Gurumurthy
Prema
P
D000995:Antitubercular Agents / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D007538:Isoniazid / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000201:enzymology*; D012293:Rifampin / Q000494:pharmacology*
D000995:Antitubercular Agents; D003577:Cytochrome P-450 Enzyme System; D007538:Isoniazid; D012293:Rifampin