Intramacrophage Mycobacterium tuberculosis efflux pump gene regulation after rifampicin and verapamil exposure

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dc.contributor.authorCanezin, Pedro Henrique
dc.contributor.authorCaleffi-Ferracioli, Katiany Rizzieri
dc.contributor.authorLima Scodro, Regiane Bertin de
dc.contributor.authorDias Siqueira, Vera Lucia
dc.contributor.authorPavan, Fernando Rogerio [UNESP]
dc.contributor.authorEsteves Barros, Isabella Leticia
dc.contributor.authorCardoso, Rosilene Fressatti
dc.contributor.institutionUniversidade Estadual de Maringá (UEM)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2018-11-29T21:58:09Z
dc.date.available2018-11-29T21:58:09Z
dc.date.issued2018-07-01
dc.description.abstractObjectives: 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.en
dc.description.affiliationUniv Estadual Maringa, Programa Posgrad Ciencias Saude, Maringa, Parana, Brazil
dc.description.affiliationUniv Estadual Maringa, Dept Anal Clin & Biomed, Maringa, Parana, Brazil
dc.description.affiliationUniv Estadual Paulista, Araraquara, SP, Brazil
dc.description.affiliationUnespUniv Estadual Paulista, Araraquara, SP, Brazil
dc.description.sponsorshipFundacao Araucaria
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent1770-1776
dc.identifierhttp://dx.doi.org/10.1093/jac/dky091
dc.identifier.citationJournal Of Antimicrobial Chemotherapy. Oxford: Oxford Univ Press, v. 73, n. 7, p. 1770-1776, 2018.
dc.identifier.doi10.1093/jac/dky091
dc.identifier.fileWOS000438375800005.pdf
dc.identifier.issn0305-7453
dc.identifier.urihttp://hdl.handle.net/11449/166245
dc.identifier.wosWOS:000438375800005
dc.language.isoeng
dc.publisherOxford Univ Press
dc.relation.ispartofJournal Of Antimicrobial Chemotherapy
dc.rights.accessRightsAcesso aberto
dc.sourceWeb of Science
dc.titleIntramacrophage Mycobacterium tuberculosis efflux pump gene regulation after rifampicin and verapamil exposureen
dc.typeArtigo
dcterms.licensehttp://www.oxfordjournals.org/access_purchase/self-archiving_policyb.html
dcterms.rightsHolderOxford Univ Press

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