Intramacrophage Mycobacterium tuberculosis efflux pump gene regulation after rifampicin and verapamil exposure
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Data
2018-07-01
Autores
Canezin, Pedro Henrique
Caleffi-Ferracioli, Katiany Rizzieri
Lima Scodro, Regiane Bertin de
Dias Siqueira, Vera Lucia
Pavan, Fernando Rogerio [UNESP]
Esteves Barros, Isabella Leticia
Cardoso, Rosilene Fressatti
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Oxford Univ Press
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Objectives: Since resistance of Mycobacteriumtuberculosis (Mtb) partially derives fromefflux pumps (EPs) in the plasma membrane, the current study evaluates EPs in Mtb exposed to rifampicin in the presence of the EP inhibitor verapamil, within a macrophage environment. Methods: Human acute monocytic leukaemia cell line THP-1 was infected with Mtb H37Rv and exposed to rifampicin and verapamil alone and in combination for 24 and 72 h. After RNA extraction, quantitative PCR was carried out for 11 EP genes using SYBR green PCR master mix in the StepOneTM Real-Time PCR System. Results: After 24 h of exposure to rifampicin, Mtb H37Rv showed that 10 EP genes were up-regulated when compared with the control. The rifampicin/verapamil combination induced down-regulation of 54.5% (6/11) of the EP genes. At 72 h, rifampicin exposure induced up-regulation of 10 EP genes and rifampicin/verapamil induced down-regulation of 8 EP genes, which suggests effective EP-inhibitory activity of verapamil against Mtb H37Rv in an intramacrophage environment. Conclusions: The current study demonstrated that rifampicin/verapamil caused down-regulation of several EP genes in Mtb inside the macrophage environment. In vivo trials may show that rifampicin/verapamil therapy could be of value in enhancing anti-TB treatment.
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Journal Of Antimicrobial Chemotherapy. Oxford: Oxford Univ Press, v. 73, n. 7, p. 1770-1776, 2018.