Modulatory effects of verapamil in rifampicin activity against Mycobacterium tuberculosis
Caleffi-Ferracioli KR, Cardoso RF, de Souza JV, Murase LS, Canezin PH, Scodro RB, Ld Siqueira V, Pavan FR
Future microbiology · 2019-01
Abstract
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.
MeSH terms
- Humans
- Mycobacterium tuberculosis
- Tuberculosis, Multidrug-Resistant
- Verapamil
- Rifampin
- Oxidoreductases
- Catalase
- DNA-Directed RNA Polymerases
- Bacterial Proteins
- Membrane Transport Proteins
- Antitubercular Agents
- Drug Therapy, Combination
- Microbial Sensitivity Tests
- Drug Resistance, Multiple, Bacterial
- Gene Expression Regulation, Bacterial
- Drug Synergism
- Genotype
- Mutation
- Time Factors
- Brazil