Morphological changes and differentially expressed efflux pump genes in Mycobacterium tuberculosis exposed to a rifampicin and verapamil combination

Bibliographic Details
Main Author: Caleffi-Ferracioli, Katiany R.
Publication Date: 2016
Other Authors: Amaral, Renata Claro R., Demitto, Fernanda O., Maltempe, Flaviane G., Canezin, Pedro Henrique, Scodro, Regiane B. L., Nakamura, Celso V., Leite, Clarice Queico F. [UNESP], Siqueira, Vera Lucia D., Cardoso, Rosilene F.
Format: Article
Language: eng
Source: Repositório Institucional da UNESP
Download full: http://dx.doi.org/10.1016/j.tube.2015.12.010
http://hdl.handle.net/11449/161372
Summary: The aim of the present study was to (i) evaluate the in vitro action of rifampicin (RIF), ethambutol or isoniazid with efflux pumps inhibitors (EPIs) in Mycobacterium tuberculosis (Mtb) H(37)Rv and (ii) evaluate the morphological and efflux pumps (EPs) transcriptional changes by the action of rifampicin + verapamil combination (RIF + VP). The minimal inhibitory concentration and synergic effect of drug combinations were determined by Resazurin Microtiter Plate Assay and Resazurin Drugs Combination Microtiter Assay, respectively. VP showed greater capacity of ethidium bromide accumulation and RIF + VP had the lower fractional inhibitory concentration index. The RIF + VP exerted a similar reduction of viable cell counts to RIF by time kill curve, but decreases in the expression of EPs genes were observed by Real time PCR at 72 h of RIF + VP exposure. Accumulative morphological changes (wrinkled and rounding) caused by each drug were observed by scanning electron microscopy after RIF + VP exposure. The downexpression of EPs related genes exposed to RIF + VP, suggest an effective inhibitory activity of VP in Mtb H(37)Rv. The role of EPs and the use of EPIs open up a powerful approach and the RIF + VP combination should be studied in Mtb more thoroughly. (c) 2016 Elsevier Ltd. All rights reserved.
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spelling Morphological changes and differentially expressed efflux pump genes in Mycobacterium tuberculosis exposed to a rifampicin and verapamil combinationMycobacterium tuberculosisEfflux pumpMorphological changesGene expressionDrug combinationsThe aim of the present study was to (i) evaluate the in vitro action of rifampicin (RIF), ethambutol or isoniazid with efflux pumps inhibitors (EPIs) in Mycobacterium tuberculosis (Mtb) H(37)Rv and (ii) evaluate the morphological and efflux pumps (EPs) transcriptional changes by the action of rifampicin + verapamil combination (RIF + VP). The minimal inhibitory concentration and synergic effect of drug combinations were determined by Resazurin Microtiter Plate Assay and Resazurin Drugs Combination Microtiter Assay, respectively. VP showed greater capacity of ethidium bromide accumulation and RIF + VP had the lower fractional inhibitory concentration index. The RIF + VP exerted a similar reduction of viable cell counts to RIF by time kill curve, but decreases in the expression of EPs genes were observed by Real time PCR at 72 h of RIF + VP exposure. Accumulative morphological changes (wrinkled and rounding) caused by each drug were observed by scanning electron microscopy after RIF + VP exposure. The downexpression of EPs related genes exposed to RIF + VP, suggest an effective inhibitory activity of VP in Mtb H(37)Rv. The role of EPs and the use of EPIs open up a powerful approach and the RIF + VP combination should be studied in Mtb more thoroughly. (c) 2016 Elsevier Ltd. All rights reserved.Fundacao AraucariaUniv Estadual Maringa, Postgrad Program Hlth Sci, BR-87020900 Maringa, Parana, BrazilUniv Estadual Maringa, Lab Med Bacteriol, Dept Clin Anal & Biomed, BR-87020900 Maringa, Parana, BrazilUniv Estadual Maringa, Dept Basic Hlth Sci, BR-87020900 Maringa, Parana, BrazilUniv Estadual Paulista, Sch Pharmaceut Sci, Dept Biol Sci, Sao Paulo, BrazilUniv Estadual Paulista, Sch Pharmaceut Sci, Dept Biol Sci, Sao Paulo, BrazilChurchill LivingstoneUniversidade Estadual de Maringá (UEM)Universidade Estadual Paulista (Unesp)Caleffi-Ferracioli, Katiany R.Amaral, Renata Claro R.Demitto, Fernanda O.Maltempe, Flaviane G.Canezin, Pedro HenriqueScodro, Regiane B. L.Nakamura, Celso V.Leite, Clarice Queico F. [UNESP]Siqueira, Vera Lucia D.Cardoso, Rosilene F.2018-11-26T16:32:28Z2018-11-26T16:32:28Z2016-03-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article65-72application/pdfhttp://dx.doi.org/10.1016/j.tube.2015.12.010Tuberculosis. Edinburgh: Churchill Livingstone, v. 97, p. 65-72, 2016.1472-9792http://hdl.handle.net/11449/16137210.1016/j.tube.2015.12.010WOS:000373538400010WOS000373538400010.pdfWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengTuberculosis1,264info:eu-repo/semantics/openAccess2023-10-20T06:09:16Zoai:repositorio.unesp.br:11449/161372Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-10-20T06:09:16Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Morphological changes and differentially expressed efflux pump genes in Mycobacterium tuberculosis exposed to a rifampicin and verapamil combination
title Morphological changes and differentially expressed efflux pump genes in Mycobacterium tuberculosis exposed to a rifampicin and verapamil combination
spellingShingle Morphological changes and differentially expressed efflux pump genes in Mycobacterium tuberculosis exposed to a rifampicin and verapamil combination
Caleffi-Ferracioli, Katiany R.
Mycobacterium tuberculosis
Efflux pump
Morphological changes
Gene expression
Drug combinations
title_short Morphological changes and differentially expressed efflux pump genes in Mycobacterium tuberculosis exposed to a rifampicin and verapamil combination
title_full Morphological changes and differentially expressed efflux pump genes in Mycobacterium tuberculosis exposed to a rifampicin and verapamil combination
title_fullStr Morphological changes and differentially expressed efflux pump genes in Mycobacterium tuberculosis exposed to a rifampicin and verapamil combination
title_full_unstemmed Morphological changes and differentially expressed efflux pump genes in Mycobacterium tuberculosis exposed to a rifampicin and verapamil combination
title_sort Morphological changes and differentially expressed efflux pump genes in Mycobacterium tuberculosis exposed to a rifampicin and verapamil combination
author Caleffi-Ferracioli, Katiany R.
author_facet Caleffi-Ferracioli, Katiany R.
Amaral, Renata Claro R.
Demitto, Fernanda O.
Maltempe, Flaviane G.
Canezin, Pedro Henrique
Scodro, Regiane B. L.
Nakamura, Celso V.
Leite, Clarice Queico F. [UNESP]
Siqueira, Vera Lucia D.
Cardoso, Rosilene F.
author_role author
author2 Amaral, Renata Claro R.
Demitto, Fernanda O.
Maltempe, Flaviane G.
Canezin, Pedro Henrique
Scodro, Regiane B. L.
Nakamura, Celso V.
Leite, Clarice Queico F. [UNESP]
Siqueira, Vera Lucia D.
Cardoso, Rosilene F.
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual de Maringá (UEM)
Universidade Estadual Paulista (Unesp)
dc.contributor.author.fl_str_mv Caleffi-Ferracioli, Katiany R.
Amaral, Renata Claro R.
Demitto, Fernanda O.
Maltempe, Flaviane G.
Canezin, Pedro Henrique
Scodro, Regiane B. L.
Nakamura, Celso V.
Leite, Clarice Queico F. [UNESP]
Siqueira, Vera Lucia D.
Cardoso, Rosilene F.
dc.subject.por.fl_str_mv Mycobacterium tuberculosis
Efflux pump
Morphological changes
Gene expression
Drug combinations
topic Mycobacterium tuberculosis
Efflux pump
Morphological changes
Gene expression
Drug combinations
description The aim of the present study was to (i) evaluate the in vitro action of rifampicin (RIF), ethambutol or isoniazid with efflux pumps inhibitors (EPIs) in Mycobacterium tuberculosis (Mtb) H(37)Rv and (ii) evaluate the morphological and efflux pumps (EPs) transcriptional changes by the action of rifampicin + verapamil combination (RIF + VP). The minimal inhibitory concentration and synergic effect of drug combinations were determined by Resazurin Microtiter Plate Assay and Resazurin Drugs Combination Microtiter Assay, respectively. VP showed greater capacity of ethidium bromide accumulation and RIF + VP had the lower fractional inhibitory concentration index. The RIF + VP exerted a similar reduction of viable cell counts to RIF by time kill curve, but decreases in the expression of EPs genes were observed by Real time PCR at 72 h of RIF + VP exposure. Accumulative morphological changes (wrinkled and rounding) caused by each drug were observed by scanning electron microscopy after RIF + VP exposure. The downexpression of EPs related genes exposed to RIF + VP, suggest an effective inhibitory activity of VP in Mtb H(37)Rv. The role of EPs and the use of EPIs open up a powerful approach and the RIF + VP combination should be studied in Mtb more thoroughly. (c) 2016 Elsevier Ltd. All rights reserved.
publishDate 2016
dc.date.none.fl_str_mv 2016-03-01
2018-11-26T16:32:28Z
2018-11-26T16:32:28Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1016/j.tube.2015.12.010
Tuberculosis. Edinburgh: Churchill Livingstone, v. 97, p. 65-72, 2016.
1472-9792
http://hdl.handle.net/11449/161372
10.1016/j.tube.2015.12.010
WOS:000373538400010
WOS000373538400010.pdf
url http://dx.doi.org/10.1016/j.tube.2015.12.010
http://hdl.handle.net/11449/161372
identifier_str_mv Tuberculosis. Edinburgh: Churchill Livingstone, v. 97, p. 65-72, 2016.
1472-9792
10.1016/j.tube.2015.12.010
WOS:000373538400010
WOS000373538400010.pdf
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Tuberculosis
1,264
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 65-72
application/pdf
dc.publisher.none.fl_str_mv Churchill Livingstone
publisher.none.fl_str_mv Churchill Livingstone
dc.source.none.fl_str_mv Web of Science
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
_version_ 1797789456686645248

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