Isoniazid and verapamil modulatory activity and efflux pump gene expression in Mycobacterium tuberculosis.
| Title: | Isoniazid and verapamil modulatory activity and efflux pump gene expression in Mycobacterium tuberculosis. |
|---|---|
| Authors: | de Souza JVP; Laboratório de Bacteriologia Médica, Universidade Estadual de Maringá, Maringá, PR.; Murase LS; Laboratório de Bacteriologia Médica, Universidade Estadual de Maringá, Maringá, PR.; Caleffi-Ferracioli KR; Laboratório de Bacteriologia Médica, Universidade Estadual de Maringá, Maringá, PR.; Palomo CT; Laboratório de Bacteriologia Médica, Universidade Estadual de Maringá, Maringá, PR.; de Lima Scodro RB; Laboratório de Bacteriologia Médica, Universidade Estadual de Maringá, Maringá, PR.; Siqueira VLD; Laboratório de Bacteriologia Médica, Universidade Estadual de Maringá, Maringá, PR.; Pavan FR; Faculdade de Ciências Farmacêuticas, Departamento de Ciências Biológicas, Universidade Estadual Paulista, Araraquara, São Paulo, SP, Brazil.; Cardoso RF; Laboratório de Bacteriologia Médica, Universidade Estadual de Maringá, Maringá, PR. |
| Source: | The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease [Int J Tuberc Lung Dis] 2020 Jun 01; Vol. 24 (6), pp. 591-596. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: International Union against Tuberculosis and Lung Disease Country of Publication: France NLM ID: 9706389 Publication Model: Print Cited Medium: Internet ISSN: 1815-7920 (Electronic) Linking ISSN: 10273719 NLM ISO Abbreviation: Int J Tuberc Lung Dis Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Paris, France : International Union against Tuberculosis and Lung Disease, c1997- |
| MeSH Terms: | Mycobacterium tuberculosis*/genetics ; Tuberculosis, Multidrug-Resistant*/drug therapy; Antitubercular Agents/pharmacology ; Bacterial Proteins/genetics ; Isoniazid/pharmacology ; Membrane Transport Proteins/genetics ; Verapamil/pharmacology ; Gene Expression ; Humans ; Microbial Sensitivity Tests ; Mutation |
| Abstract: | INTRODUCTION: Resistance to first-line anti-tuberculosis drugs is a major concern in the treatment of the disease. New strategies, such as the use of efflux pump inhibitors (EPIs), are being investigated to improve the outcome of the treatment. Verapamil (VP), one such inhibitor, was shown to inhibit several efflux pump (EP) Mycobacterium tuberculosis proteins and demonstrate synergic activity with anti-TB drugs.OBJECTIVE: To evaluate the combinatory effect of isoniazid (INH) and VP in M. tuberculosis.METHODS: Minimal inhibitory concentrations and combinatory effects of INH+VP were determined using respectively resazurin microtitre assay plate (REMA) and resazurin drugs combination microtitre assay (REDCA). From the results, we selected three bacilli with different susceptibility profiles and assessed their expression of 10 EP genes through quantitative reverse transcription polymerase chain reaction after exposure to INH, VP and INH + VP for 48 h.RESULTS: A significant reduction of INH MIC was observed in INH-susceptible isolates upon combination with VP. In brief, gene expression assays revealed expression patterns that could be correlated with each resistance profile, presence or absence of gene mutations and combinatory effect with VP.CONCLUSION: Combining VP with INH showed important results in drug-susceptible strains, and clinical trials on combined VP + anti-TB drugs should be discussed. |
| Substance Nomenclature: | 0 (Antitubercular Agents); 0 (Bacterial Proteins); 0 (Membrane Transport Proteins); CJ0O37KU29 (Verapamil); V83O1VOZ8L (Isoniazid) |
| Entry Date(s): | Date Created: 20200620 Date Completed: 20210427 Latest Revision: 20210427 |
| Update Code: | 20260130 |
| DOI: | 10.5588/ijtld.19.0458 |
| PMID: | 32553016 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't