Rescue of streptomycin activity by piperine in Mycobacterium tuberculosis.

Aim: To evaluate the modulatory effect of piperine (PIP) on streptomycin (SM) activity in Mycobacterium tuberculosis (Mtb). Materials & methods: SM and PIP minimum inhibitory concentration (MIC) and combinatory activity were determined in Mtb H37Rv and in susceptible and resistant clinical isolates. Ethidium bromide accumulation assay and relative quantification of efflux pumps genes (rv1258c, rv1218c and rv2942), after SM and SM+PIP combination exposure, were also performed. Results: PIP concentration of 25 µg/ml (1/4× MIC) was able to inhibit efflux pumps activity, to modulate SM activity in Mtb, and conducted changes in the relative quantification of efflux pumps genes. Conclusion: SM+PIP combination was able to rescue the SM-susceptible MIC values in SM-resistant Mtb.

Modulatory effects of verapamil in rifampicin activity against Mycobacterium tuberculosis.

AIM: To evaluate modulatory effect of verapamil (VP) in rifampicin (RIF) activity and its effect in efflux pumps (EPs) transcript levels in Mycobacterium tuberculosis. MATERIALS & METHODS: RIF and VP minimal inhibitory concentration, combinatory effect and detection of mutations were determined in 16 isolates. EPs transcript levels were determined in four isolates by real-time PCR after exposure to drugs. RESULTS: VP showed good combinatory effect among RIF-resistant isolates. This effect was also observed in the relative transcript levels of EPs, mainly after 72 h of exposure, depending on the EP gene, genotype and the resistance profile of the isolate. CONCLUSION: Additional regulatory mechanisms in the EP activities, as well as, interactions with other drug-specific resistance mechanisms need further investigation in M. tuberculosis.