The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network

Autores
Venturi, Veronica; Davies, Carolina; Singh, Jonathan A.; Matthews, James H.; Bellows, David S.; Northcote, Peter T.; Keyzers, Robert A.; Teesdale Spittle, Paul
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The mycalamides belong to a family of protein synthesis inhibitors noted for antifungal, antitumour, antiviral, immunosuppressive, and nematocidal activities. Here we report a systematic analysis of the role of drug efflux pumps in mycalamide resistance and the first isolation ofmycalamide E. In human cell lines, neither P-glycoprotein overexpression nor the use of efflux pump inhibitors significantly modulated mycalamide A toxicity in the systems tested. In Saccharomyces cerevisiae, it appears thatmycalamide A is subject to efflux by the principle mediator of xenobiotic efflux, Pdr5p alongwith the major facilitator superfamily pump Tpo1p. Mycalamide E showed a similar efflux profile. These results suggest that future drugs based on the mycalamides are likely to be valuable in situations where efflux pump?based resistance leads to failure of other chemotherapeutic approaches, although efflux may be a mediator of resistance in antifungal applications.
Fil: Venturi, Veronica. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
Fil: Davies, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Cs.de la Salud. Instituto de Patología Experimental; Argentina. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
Fil: Singh, Jonathan A.. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
Fil: Matthews, James H.. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
Fil: Bellows, David S.. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
Fil: Northcote, Peter T.. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
Fil: Keyzers, Robert A.. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
Fil: Teesdale Spittle, Paul. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
Materia
Mycalamide
Efflux
Pdr
Resistance
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/16714
Acceder
id CONICETDig_006d149cd9c7d67812055ff8cb61f0b5
oai_identifier_str oai:ri.conicet.gov.ar:11336/16714
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux networkVenturi, VeronicaDavies, CarolinaSingh, Jonathan A.Matthews, James H.Bellows, David S.Northcote, Peter T.Keyzers, Robert A.Teesdale Spittle, PaulMycalamideEffluxPdrResistancehttps://purl.org/becyt/ford/1.7https://purl.org/becyt/ford/1The mycalamides belong to a family of protein synthesis inhibitors noted for antifungal, antitumour, antiviral, immunosuppressive, and nematocidal activities. Here we report a systematic analysis of the role of drug efflux pumps in mycalamide resistance and the first isolation ofmycalamide E. In human cell lines, neither P-glycoprotein overexpression nor the use of efflux pump inhibitors significantly modulated mycalamide A toxicity in the systems tested. In Saccharomyces cerevisiae, it appears thatmycalamide A is subject to efflux by the principle mediator of xenobiotic efflux, Pdr5p alongwith the major facilitator superfamily pump Tpo1p. Mycalamide E showed a similar efflux profile. These results suggest that future drugs based on the mycalamides are likely to be valuable in situations where efflux pump?based resistance leads to failure of other chemotherapeutic approaches, although efflux may be a mediator of resistance in antifungal applications.Fil: Venturi, Veronica. Victoria University of Wellington. Centre for Biodiscovery; Nueva ZelandaFil: Davies, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Cs.de la Salud. Instituto de Patología Experimental; Argentina. Victoria University of Wellington. Centre for Biodiscovery; Nueva ZelandaFil: Singh, Jonathan A.. Victoria University of Wellington. Centre for Biodiscovery; Nueva ZelandaFil: Matthews, James H.. Victoria University of Wellington. Centre for Biodiscovery; Nueva ZelandaFil: Bellows, David S.. Victoria University of Wellington. Centre for Biodiscovery; Nueva ZelandaFil: Northcote, Peter T.. Victoria University of Wellington. Centre for Biodiscovery; Nueva ZelandaFil: Keyzers, Robert A.. Victoria University of Wellington. Centre for Biodiscovery; Nueva ZelandaFil: Teesdale Spittle, Paul. Victoria University of Wellington. Centre for Biodiscovery; Nueva ZelandaJohn Wiley & Sons Inc2012-03-20info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/16714Venturi, Veronica; Davies, Carolina; Singh, Jonathan A.; Matthews, James H.; Bellows, David S.; et al.; The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network; John Wiley & Sons Inc; Journal Of Biochemical And Molecular Toxicology; 26; 3; 20-3-2012; 94-1001095-6670enginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/jbt.20414/fullinfo:eu-repo/semantics/altIdentifier/doi/10.1002/jbt.20414info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:19:51Zoai:ri.conicet.gov.ar:11336/16714instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:19:51.516CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network
title The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network
spellingShingle The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network
Venturi, Veronica
Mycalamide
Efflux
Pdr
Resistance
title_short The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network
title_full The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network
title_fullStr The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network
title_full_unstemmed The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network
title_sort The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network
dc.creator.none.fl_str_mv Venturi, Veronica
Davies, Carolina
Singh, Jonathan A.
Matthews, James H.
Bellows, David S.
Northcote, Peter T.
Keyzers, Robert A.
Teesdale Spittle, Paul
author Venturi, Veronica
author_facet Venturi, Veronica
Davies, Carolina
Singh, Jonathan A.
Matthews, James H.
Bellows, David S.
Northcote, Peter T.
Keyzers, Robert A.
Teesdale Spittle, Paul
author_role author
author2 Davies, Carolina
Singh, Jonathan A.
Matthews, James H.
Bellows, David S.
Northcote, Peter T.
Keyzers, Robert A.
Teesdale Spittle, Paul
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Mycalamide
Efflux
Pdr
Resistance
topic Mycalamide
Efflux
Pdr
Resistance
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.7
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The mycalamides belong to a family of protein synthesis inhibitors noted for antifungal, antitumour, antiviral, immunosuppressive, and nematocidal activities. Here we report a systematic analysis of the role of drug efflux pumps in mycalamide resistance and the first isolation ofmycalamide E. In human cell lines, neither P-glycoprotein overexpression nor the use of efflux pump inhibitors significantly modulated mycalamide A toxicity in the systems tested. In Saccharomyces cerevisiae, it appears thatmycalamide A is subject to efflux by the principle mediator of xenobiotic efflux, Pdr5p alongwith the major facilitator superfamily pump Tpo1p. Mycalamide E showed a similar efflux profile. These results suggest that future drugs based on the mycalamides are likely to be valuable in situations where efflux pump?based resistance leads to failure of other chemotherapeutic approaches, although efflux may be a mediator of resistance in antifungal applications.
Fil: Venturi, Veronica. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
Fil: Davies, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Cs.de la Salud. Instituto de Patología Experimental; Argentina. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
Fil: Singh, Jonathan A.. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
Fil: Matthews, James H.. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
Fil: Bellows, David S.. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
Fil: Northcote, Peter T.. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
Fil: Keyzers, Robert A.. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
Fil: Teesdale Spittle, Paul. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
description The mycalamides belong to a family of protein synthesis inhibitors noted for antifungal, antitumour, antiviral, immunosuppressive, and nematocidal activities. Here we report a systematic analysis of the role of drug efflux pumps in mycalamide resistance and the first isolation ofmycalamide E. In human cell lines, neither P-glycoprotein overexpression nor the use of efflux pump inhibitors significantly modulated mycalamide A toxicity in the systems tested. In Saccharomyces cerevisiae, it appears thatmycalamide A is subject to efflux by the principle mediator of xenobiotic efflux, Pdr5p alongwith the major facilitator superfamily pump Tpo1p. Mycalamide E showed a similar efflux profile. These results suggest that future drugs based on the mycalamides are likely to be valuable in situations where efflux pump?based resistance leads to failure of other chemotherapeutic approaches, although efflux may be a mediator of resistance in antifungal applications.
publishDate 2012
dc.date.none.fl_str_mv 2012-03-20
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/16714
Venturi, Veronica; Davies, Carolina; Singh, Jonathan A.; Matthews, James H.; Bellows, David S.; et al.; The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network; John Wiley & Sons Inc; Journal Of Biochemical And Molecular Toxicology; 26; 3; 20-3-2012; 94-100
1095-6670
url http://hdl.handle.net/11336/16714
identifier_str_mv Venturi, Veronica; Davies, Carolina; Singh, Jonathan A.; Matthews, James H.; Bellows, David S.; et al.; The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network; John Wiley & Sons Inc; Journal Of Biochemical And Molecular Toxicology; 26; 3; 20-3-2012; 94-100
1095-6670
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/jbt.20414/full
info:eu-repo/semantics/altIdentifier/doi/10.1002/jbt.20414
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv John Wiley & Sons Inc
publisher.none.fl_str_mv John Wiley & Sons Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846781681035378688
score 12.982451

Publicaciones similares