The role of efflux pumps in Schistosoma mansoni Praziquantel resistant phenotype
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://doi.org/10.1371/journal.pone.0140147 |
Resumo: | Background: Schistosomiasis is a neglected disease caused by a trematode of the genus Schistosoma that is second only to malaria in public health significance in Africa, South America, and Asia. Praziquantel (PZQ) is the drug of choice to treat this disease due to its high cure rates and no significant side effects. However, in the last years increasingly cases of tolerance to PZQ have been reported, which has caused growing concerns regarding the emergency of resistance to this drug. Methodology/Principal Findings: Here we describe the selection of a parasitic strain that has a stable resistance phenotype to PZQ. It has been reported that drug resistance in helminths might involve efflux pumps such as members of ATP-binding cassette transport proteins, including P-glycoprotein and multidrug resistance-associated protein families. Here we evaluate the role of efflux pumps in Schistosoma mansoni resistance to PZQ, by comparing the efflux pumps activity in susceptible and resistant strains. The evaluation of the efflux activity was performed by an ethidium bromide accumulation assay in presence and absence of Verapamil. The role of efflux pumps in resistance to PZQ was further investigated comparing the response of susceptible and resistant parasites in the absence and presence of different doses of Verapamil, in an ex vivo assay, and these results were further reinforced through the comparison of the expression levels of SmMDR2 RNA by RT-PCR. Conclusions/Significance: This work strongly suggests the involvement of Pgp-like transporters SMDR2 in Praziquantel drug resistance in S. mansoni. Low doses of Verapamil successfully reverted drug resistance. Our results might give an indication that a combination therapy with PZQ and natural or synthetic Pgp modulators can be an effective strategy for the treatment of confirmed cases of resistance to PZQ in S. mansoni. |
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The role of efflux pumps in Schistosoma mansoni Praziquantel resistant phenotypeBiochemistry, Genetics and Molecular Biology (miscellaneous)Infectious DiseasesParasitologyDrug DiscoverySDG 3 - Good Health and Well-beingBackground: Schistosomiasis is a neglected disease caused by a trematode of the genus Schistosoma that is second only to malaria in public health significance in Africa, South America, and Asia. Praziquantel (PZQ) is the drug of choice to treat this disease due to its high cure rates and no significant side effects. However, in the last years increasingly cases of tolerance to PZQ have been reported, which has caused growing concerns regarding the emergency of resistance to this drug. Methodology/Principal Findings: Here we describe the selection of a parasitic strain that has a stable resistance phenotype to PZQ. It has been reported that drug resistance in helminths might involve efflux pumps such as members of ATP-binding cassette transport proteins, including P-glycoprotein and multidrug resistance-associated protein families. Here we evaluate the role of efflux pumps in Schistosoma mansoni resistance to PZQ, by comparing the efflux pumps activity in susceptible and resistant strains. The evaluation of the efflux activity was performed by an ethidium bromide accumulation assay in presence and absence of Verapamil. The role of efflux pumps in resistance to PZQ was further investigated comparing the response of susceptible and resistant parasites in the absence and presence of different doses of Verapamil, in an ex vivo assay, and these results were further reinforced through the comparison of the expression levels of SmMDR2 RNA by RT-PCR. Conclusions/Significance: This work strongly suggests the involvement of Pgp-like transporters SMDR2 in Praziquantel drug resistance in S. mansoni. Low doses of Verapamil successfully reverted drug resistance. Our results might give an indication that a combination therapy with PZQ and natural or synthetic Pgp modulators can be an effective strategy for the treatment of confirmed cases of resistance to PZQ in S. mansoni.Instituto de Higiene e Medicina Tropical (IHMT)Global Health and Tropical Medicine (GHTM)TB, HIV and opportunistic diseases and pathogens (THOP)Vector borne diseases and pathogens (VBD)RUNPinto-Almeida, AntónioMendes, TiagoArmada, AnaBelo, SilvanaCarrilho, EmanuelViveiros, MiguelAfonso, Ana2018-05-11T22:03:07Z2015-10-072015-10-07T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article20application/pdfhttps://doi.org/10.1371/journal.pone.0140147eng1932-6203PURE: 1730306http://www.scopus.com/inward/record.url?scp=84948692444&partnerID=8YFLogxKhttps://doi.org/10.1371/journal.pone.0140147info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:20:03Zoai:run.unl.pt:10362/36593Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:30:34.629228Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
The role of efflux pumps in Schistosoma mansoni Praziquantel resistant phenotype |
title |
The role of efflux pumps in Schistosoma mansoni Praziquantel resistant phenotype |
spellingShingle |
The role of efflux pumps in Schistosoma mansoni Praziquantel resistant phenotype Pinto-Almeida, António Biochemistry, Genetics and Molecular Biology (miscellaneous) Infectious Diseases Parasitology Drug Discovery SDG 3 - Good Health and Well-being |
title_short |
The role of efflux pumps in Schistosoma mansoni Praziquantel resistant phenotype |
title_full |
The role of efflux pumps in Schistosoma mansoni Praziquantel resistant phenotype |
title_fullStr |
The role of efflux pumps in Schistosoma mansoni Praziquantel resistant phenotype |
title_full_unstemmed |
The role of efflux pumps in Schistosoma mansoni Praziquantel resistant phenotype |
title_sort |
The role of efflux pumps in Schistosoma mansoni Praziquantel resistant phenotype |
author |
Pinto-Almeida, António |
author_facet |
Pinto-Almeida, António Mendes, Tiago Armada, Ana Belo, Silvana Carrilho, Emanuel Viveiros, Miguel Afonso, Ana |
author_role |
author |
author2 |
Mendes, Tiago Armada, Ana Belo, Silvana Carrilho, Emanuel Viveiros, Miguel Afonso, Ana |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Instituto de Higiene e Medicina Tropical (IHMT) Global Health and Tropical Medicine (GHTM) TB, HIV and opportunistic diseases and pathogens (THOP) Vector borne diseases and pathogens (VBD) RUN |
dc.contributor.author.fl_str_mv |
Pinto-Almeida, António Mendes, Tiago Armada, Ana Belo, Silvana Carrilho, Emanuel Viveiros, Miguel Afonso, Ana |
dc.subject.por.fl_str_mv |
Biochemistry, Genetics and Molecular Biology (miscellaneous) Infectious Diseases Parasitology Drug Discovery SDG 3 - Good Health and Well-being |
topic |
Biochemistry, Genetics and Molecular Biology (miscellaneous) Infectious Diseases Parasitology Drug Discovery SDG 3 - Good Health and Well-being |
description |
Background: Schistosomiasis is a neglected disease caused by a trematode of the genus Schistosoma that is second only to malaria in public health significance in Africa, South America, and Asia. Praziquantel (PZQ) is the drug of choice to treat this disease due to its high cure rates and no significant side effects. However, in the last years increasingly cases of tolerance to PZQ have been reported, which has caused growing concerns regarding the emergency of resistance to this drug. Methodology/Principal Findings: Here we describe the selection of a parasitic strain that has a stable resistance phenotype to PZQ. It has been reported that drug resistance in helminths might involve efflux pumps such as members of ATP-binding cassette transport proteins, including P-glycoprotein and multidrug resistance-associated protein families. Here we evaluate the role of efflux pumps in Schistosoma mansoni resistance to PZQ, by comparing the efflux pumps activity in susceptible and resistant strains. The evaluation of the efflux activity was performed by an ethidium bromide accumulation assay in presence and absence of Verapamil. The role of efflux pumps in resistance to PZQ was further investigated comparing the response of susceptible and resistant parasites in the absence and presence of different doses of Verapamil, in an ex vivo assay, and these results were further reinforced through the comparison of the expression levels of SmMDR2 RNA by RT-PCR. Conclusions/Significance: This work strongly suggests the involvement of Pgp-like transporters SMDR2 in Praziquantel drug resistance in S. mansoni. Low doses of Verapamil successfully reverted drug resistance. Our results might give an indication that a combination therapy with PZQ and natural or synthetic Pgp modulators can be an effective strategy for the treatment of confirmed cases of resistance to PZQ in S. mansoni. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-10-07 2015-10-07T00:00:00Z 2018-05-11T22:03:07Z |
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 |
https://doi.org/10.1371/journal.pone.0140147 |
url |
https://doi.org/10.1371/journal.pone.0140147 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1932-6203 PURE: 1730306 http://www.scopus.com/inward/record.url?scp=84948692444&partnerID=8YFLogxK https://doi.org/10.1371/journal.pone.0140147 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
20 application/pdf |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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