Microbial Efflux Systems and Inhibitors: Approaches to Drug Discovery and the Challenge of Clinical Implementation

Autores
Kourtesi, Christina; Ball, Anthony R.; Huan, Ying-Ying; Jachak, Sanjay M.; Vera, Domingo Mariano Adolfo; Khondkar, Proma; Gibbons, Simon; Hamblin, Michael R.; Tegos, George P.
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Conventional antimicrobials are increasingly ineffective due to the emergence of multidrug-resistance among pathogenic microorganisms. The need to overcome these deficiencies has triggered exploration for novel and unconventional approaches to controlling microbial infections. Multidrug efflux systems (MES) have been a profound obstacle in the successful deployment of antimicrobials. The discovery of small molecule efflux system blockers has been an active and rapidly expanding research discipline. A major theme in this platform involves efflux pump inhibitors (EPIs) from natural sources. The discovery methodologies and the available number of natural EPI-chemotypes are increasing. Advances in our understanding of microbial physiology have shed light on a series of pathways and phenotypes where the role of efflux systems is pivotal. Complementing existing antimicrobial discovery platforms such as photodynamic therapy (PDT) with efflux inhibition is a subject under investigation. This core information is a stepping stone in the challenge of highlighting an effective drug development path for EPIs since the puzzle of clinical implementation remains unsolved. This review summarizes advances in the path of EPI discovery, discusses potential avenues of EPI implementation and development, and underlines the need for highly informative and comprehensive translational approaches.
Fil: Kourtesi, Christina. University Of New Mexico; Estados Unidos. Universidad Nacional y Kapodistriaca de Atenas; Grecia
Fil: Ball, Anthony R.. Toxikon Corp. Bedford; Estados Unidos
Fil: Huan, Ying-Ying. Harvard Medical School; Estados Unidos. Massachusetts General Hospital; Estados Unidos
Fil: Jachak, Sanjay M.. National Institute of Pharmaceutical Education and Research; India
Fil: Vera, Domingo Mariano Adolfo. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Khondkar, Proma. UCL School of Pharmacy; Reino Unido
Fil: Gibbons, Simon. UCL School of Pharmacy; Reino Unido
Fil: Hamblin, Michael R.. Harvard Medical School; Estados Unidos. Massachusetts General Hospital; Estados Unidos. Harvard-MIT Division of Health Sciences and Technology; Estados Unidos
Fil: Tegos, George P.. University Of New Mexico; Estados Unidos. Harvard Medical School; Estados Unidos. Massachusetts General Hospital; Estados Unidos. University Of New Mexico; Estados Unidos
Materia
Antimicrobial resistance
multidrug efflux systems
natural efflux pump inhibitors
photo inactivation
dual action antimicrobials
biofilm
virulence
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:11336/25878
Acceder
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spelling Microbial Efflux Systems and Inhibitors: Approaches to Drug Discovery and the Challenge of Clinical ImplementationKourtesi, ChristinaBall, Anthony R.Huan, Ying-YingJachak, Sanjay M.Vera, Domingo Mariano AdolfoKhondkar, PromaGibbons, SimonHamblin, Michael R.Tegos, George P.Antimicrobial resistancemultidrug efflux systemsnatural efflux pump inhibitorsphoto inactivationdual action antimicrobialsbiofilmvirulenceConventional antimicrobials are increasingly ineffective due to the emergence of multidrug-resistance among pathogenic microorganisms. The need to overcome these deficiencies has triggered exploration for novel and unconventional approaches to controlling microbial infections. Multidrug efflux systems (MES) have been a profound obstacle in the successful deployment of antimicrobials. The discovery of small molecule efflux system blockers has been an active and rapidly expanding research discipline. A major theme in this platform involves efflux pump inhibitors (EPIs) from natural sources. The discovery methodologies and the available number of natural EPI-chemotypes are increasing. Advances in our understanding of microbial physiology have shed light on a series of pathways and phenotypes where the role of efflux systems is pivotal. Complementing existing antimicrobial discovery platforms such as photodynamic therapy (PDT) with efflux inhibition is a subject under investigation. This core information is a stepping stone in the challenge of highlighting an effective drug development path for EPIs since the puzzle of clinical implementation remains unsolved. This review summarizes advances in the path of EPI discovery, discusses potential avenues of EPI implementation and development, and underlines the need for highly informative and comprehensive translational approaches.Fil: Kourtesi, Christina. University Of New Mexico; Estados Unidos. Universidad Nacional y Kapodistriaca de Atenas; GreciaFil: Ball, Anthony R.. Toxikon Corp. Bedford; Estados UnidosFil: Huan, Ying-Ying. Harvard Medical School; Estados Unidos. Massachusetts General Hospital; Estados UnidosFil: Jachak, Sanjay M.. National Institute of Pharmaceutical Education and Research; IndiaFil: Vera, Domingo Mariano Adolfo. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Khondkar, Proma. UCL School of Pharmacy; Reino UnidoFil: Gibbons, Simon. UCL School of Pharmacy; Reino UnidoFil: Hamblin, Michael R.. Harvard Medical School; Estados Unidos. Massachusetts General Hospital; Estados Unidos. Harvard-MIT Division of Health Sciences and Technology; Estados UnidosFil: Tegos, George P.. University Of New Mexico; Estados Unidos. Harvard Medical School; Estados Unidos. Massachusetts General Hospital; Estados Unidos. University Of New Mexico; Estados UnidosBentham Open2013-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/25878Kourtesi, Christina; Ball, Anthony R.; Huan, Ying-Ying; Jachak, Sanjay M.; Vera, Domingo Mariano Adolfo; et al.; Microbial Efflux Systems and Inhibitors: Approaches to Drug Discovery and the Challenge of Clinical Implementation ; Bentham Open; The Open Microbiology Journal; 7; Suppl 1; 6-2013; 34-521874-2858CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.2174/1874285801307010034info:eu-repo/semantics/altIdentifier/url/https://benthamopen.com/ABSTRACT/TOMICROJ-7-34info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:35:41Zoai:ri.conicet.gov.ar:11336/25878instacron: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:34982025-09-29 10:35:42.024CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Microbial Efflux Systems and Inhibitors: Approaches to Drug Discovery and the Challenge of Clinical Implementation
title Microbial Efflux Systems and Inhibitors: Approaches to Drug Discovery and the Challenge of Clinical Implementation
spellingShingle Microbial Efflux Systems and Inhibitors: Approaches to Drug Discovery and the Challenge of Clinical Implementation
Kourtesi, Christina
Antimicrobial resistance
multidrug efflux systems
natural efflux pump inhibitors
photo inactivation
dual action antimicrobials
biofilm
virulence
title_short Microbial Efflux Systems and Inhibitors: Approaches to Drug Discovery and the Challenge of Clinical Implementation
title_full Microbial Efflux Systems and Inhibitors: Approaches to Drug Discovery and the Challenge of Clinical Implementation
title_fullStr Microbial Efflux Systems and Inhibitors: Approaches to Drug Discovery and the Challenge of Clinical Implementation
title_full_unstemmed Microbial Efflux Systems and Inhibitors: Approaches to Drug Discovery and the Challenge of Clinical Implementation
title_sort Microbial Efflux Systems and Inhibitors: Approaches to Drug Discovery and the Challenge of Clinical Implementation
dc.creator.none.fl_str_mv Kourtesi, Christina
Ball, Anthony R.
Huan, Ying-Ying
Jachak, Sanjay M.
Vera, Domingo Mariano Adolfo
Khondkar, Proma
Gibbons, Simon
Hamblin, Michael R.
Tegos, George P.
author Kourtesi, Christina
author_facet Kourtesi, Christina
Ball, Anthony R.
Huan, Ying-Ying
Jachak, Sanjay M.
Vera, Domingo Mariano Adolfo
Khondkar, Proma
Gibbons, Simon
Hamblin, Michael R.
Tegos, George P.
author_role author
author2 Ball, Anthony R.
Huan, Ying-Ying
Jachak, Sanjay M.
Vera, Domingo Mariano Adolfo
Khondkar, Proma
Gibbons, Simon
Hamblin, Michael R.
Tegos, George P.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Antimicrobial resistance
multidrug efflux systems
natural efflux pump inhibitors
photo inactivation
dual action antimicrobials
biofilm
virulence
topic Antimicrobial resistance
multidrug efflux systems
natural efflux pump inhibitors
photo inactivation
dual action antimicrobials
biofilm
virulence
dc.description.none.fl_txt_mv Conventional antimicrobials are increasingly ineffective due to the emergence of multidrug-resistance among pathogenic microorganisms. The need to overcome these deficiencies has triggered exploration for novel and unconventional approaches to controlling microbial infections. Multidrug efflux systems (MES) have been a profound obstacle in the successful deployment of antimicrobials. The discovery of small molecule efflux system blockers has been an active and rapidly expanding research discipline. A major theme in this platform involves efflux pump inhibitors (EPIs) from natural sources. The discovery methodologies and the available number of natural EPI-chemotypes are increasing. Advances in our understanding of microbial physiology have shed light on a series of pathways and phenotypes where the role of efflux systems is pivotal. Complementing existing antimicrobial discovery platforms such as photodynamic therapy (PDT) with efflux inhibition is a subject under investigation. This core information is a stepping stone in the challenge of highlighting an effective drug development path for EPIs since the puzzle of clinical implementation remains unsolved. This review summarizes advances in the path of EPI discovery, discusses potential avenues of EPI implementation and development, and underlines the need for highly informative and comprehensive translational approaches.
Fil: Kourtesi, Christina. University Of New Mexico; Estados Unidos. Universidad Nacional y Kapodistriaca de Atenas; Grecia
Fil: Ball, Anthony R.. Toxikon Corp. Bedford; Estados Unidos
Fil: Huan, Ying-Ying. Harvard Medical School; Estados Unidos. Massachusetts General Hospital; Estados Unidos
Fil: Jachak, Sanjay M.. National Institute of Pharmaceutical Education and Research; India
Fil: Vera, Domingo Mariano Adolfo. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Khondkar, Proma. UCL School of Pharmacy; Reino Unido
Fil: Gibbons, Simon. UCL School of Pharmacy; Reino Unido
Fil: Hamblin, Michael R.. Harvard Medical School; Estados Unidos. Massachusetts General Hospital; Estados Unidos. Harvard-MIT Division of Health Sciences and Technology; Estados Unidos
Fil: Tegos, George P.. University Of New Mexico; Estados Unidos. Harvard Medical School; Estados Unidos. Massachusetts General Hospital; Estados Unidos. University Of New Mexico; Estados Unidos
description Conventional antimicrobials are increasingly ineffective due to the emergence of multidrug-resistance among pathogenic microorganisms. The need to overcome these deficiencies has triggered exploration for novel and unconventional approaches to controlling microbial infections. Multidrug efflux systems (MES) have been a profound obstacle in the successful deployment of antimicrobials. The discovery of small molecule efflux system blockers has been an active and rapidly expanding research discipline. A major theme in this platform involves efflux pump inhibitors (EPIs) from natural sources. The discovery methodologies and the available number of natural EPI-chemotypes are increasing. Advances in our understanding of microbial physiology have shed light on a series of pathways and phenotypes where the role of efflux systems is pivotal. Complementing existing antimicrobial discovery platforms such as photodynamic therapy (PDT) with efflux inhibition is a subject under investigation. This core information is a stepping stone in the challenge of highlighting an effective drug development path for EPIs since the puzzle of clinical implementation remains unsolved. This review summarizes advances in the path of EPI discovery, discusses potential avenues of EPI implementation and development, and underlines the need for highly informative and comprehensive translational approaches.
publishDate 2013
dc.date.none.fl_str_mv 2013-06
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/11336/25878
Kourtesi, Christina; Ball, Anthony R.; Huan, Ying-Ying; Jachak, Sanjay M.; Vera, Domingo Mariano Adolfo; et al.; Microbial Efflux Systems and Inhibitors: Approaches to Drug Discovery and the Challenge of Clinical Implementation ; Bentham Open; The Open Microbiology Journal; 7; Suppl 1; 6-2013; 34-52
1874-2858
CONICET Digital
CONICET
url http://hdl.handle.net/11336/25878
identifier_str_mv Kourtesi, Christina; Ball, Anthony R.; Huan, Ying-Ying; Jachak, Sanjay M.; Vera, Domingo Mariano Adolfo; et al.; Microbial Efflux Systems and Inhibitors: Approaches to Drug Discovery and the Challenge of Clinical Implementation ; Bentham Open; The Open Microbiology Journal; 7; Suppl 1; 6-2013; 34-52
1874-2858
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.2174/1874285801307010034
info:eu-repo/semantics/altIdentifier/url/https://benthamopen.com/ABSTRACT/TOMICROJ-7-34
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 Bentham Open
publisher.none.fl_str_mv Bentham Open
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
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score 13.070432

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