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A Microfluidic Device for Simple and Rapid Evaluation of Multidrug Efflux Pump Inhibitors

Recently, multidrug-resistant pathogens have disseminated widely owing essentially to their increased multidrug efflux pump activity. Presently, there is a scarcity of new antibacterial agents, and hence, inhibitors of multidrug efflux pumps belonging to the resistance–nodulation–cell division (RND)...

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Detalles Bibliográficos
Autores principales: Iino, Ryota, Nishino, Kunihiko, Noji, Hiroyuki, Yamaguchi, Akihito, Matsumoto, Yoshimi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Research Foundation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3274760/
https://www.ncbi.nlm.nih.gov/pubmed/22347225
http://dx.doi.org/10.3389/fmicb.2012.00040
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author Iino, Ryota
Nishino, Kunihiko
Noji, Hiroyuki
Yamaguchi, Akihito
Matsumoto, Yoshimi
author_facet Iino, Ryota
Nishino, Kunihiko
Noji, Hiroyuki
Yamaguchi, Akihito
Matsumoto, Yoshimi
author_sort Iino, Ryota
collection PubMed
description Recently, multidrug-resistant pathogens have disseminated widely owing essentially to their increased multidrug efflux pump activity. Presently, there is a scarcity of new antibacterial agents, and hence, inhibitors of multidrug efflux pumps belonging to the resistance–nodulation–cell division (RND) family appear useful in the treatment of infections by multidrug-resistant pathogens. Moreover, recent progress in microfabrication technologies has expanded the application of nano/micro-devices to the field of human healthcare, such as the detection of infections and diagnosis of diseases. We developed a microfluidic channel device for a simple and rapid evaluation of bacterial drug efflux activity. By combining the microfluidic device with a fluorogenic compound, fluorescein-di-β-D-galactopyranoside, which is hydrolyzed to a fluorescent dye in the cytoplasm of Escherichia coli, we successfully evaluated the effects of inhibitors on the RND-type multidrug efflux pumps MexAB–OprM and MexXY–OprM from Pseudomonas aeruginosa in E. coli. Our new method successfully detected the MexB-specific inhibitory effect of D13-9001 and revealed an unexpected membrane-permeabilizing effect of Phe-Arg-β-naphthylamide, which has long been used as an efflux pump inhibitor.
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spelling pubmed-32747602012-02-16 A Microfluidic Device for Simple and Rapid Evaluation of Multidrug Efflux Pump Inhibitors Iino, Ryota Nishino, Kunihiko Noji, Hiroyuki Yamaguchi, Akihito Matsumoto, Yoshimi Front Microbiol Microbiology Recently, multidrug-resistant pathogens have disseminated widely owing essentially to their increased multidrug efflux pump activity. Presently, there is a scarcity of new antibacterial agents, and hence, inhibitors of multidrug efflux pumps belonging to the resistance–nodulation–cell division (RND) family appear useful in the treatment of infections by multidrug-resistant pathogens. Moreover, recent progress in microfabrication technologies has expanded the application of nano/micro-devices to the field of human healthcare, such as the detection of infections and diagnosis of diseases. We developed a microfluidic channel device for a simple and rapid evaluation of bacterial drug efflux activity. By combining the microfluidic device with a fluorogenic compound, fluorescein-di-β-D-galactopyranoside, which is hydrolyzed to a fluorescent dye in the cytoplasm of Escherichia coli, we successfully evaluated the effects of inhibitors on the RND-type multidrug efflux pumps MexAB–OprM and MexXY–OprM from Pseudomonas aeruginosa in E. coli. Our new method successfully detected the MexB-specific inhibitory effect of D13-9001 and revealed an unexpected membrane-permeabilizing effect of Phe-Arg-β-naphthylamide, which has long been used as an efflux pump inhibitor. Frontiers Research Foundation 2012-02-08 /pmc/articles/PMC3274760/ /pubmed/22347225 http://dx.doi.org/10.3389/fmicb.2012.00040 Text en Copyright © 2012 Iino, Nishino, Noji, Yamaguchi and Matsumoto. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
spellingShingle Microbiology
Iino, Ryota
Nishino, Kunihiko
Noji, Hiroyuki
Yamaguchi, Akihito
Matsumoto, Yoshimi
A Microfluidic Device for Simple and Rapid Evaluation of Multidrug Efflux Pump Inhibitors
title A Microfluidic Device for Simple and Rapid Evaluation of Multidrug Efflux Pump Inhibitors
title_full A Microfluidic Device for Simple and Rapid Evaluation of Multidrug Efflux Pump Inhibitors
title_fullStr A Microfluidic Device for Simple and Rapid Evaluation of Multidrug Efflux Pump Inhibitors
title_full_unstemmed A Microfluidic Device for Simple and Rapid Evaluation of Multidrug Efflux Pump Inhibitors
title_short A Microfluidic Device for Simple and Rapid Evaluation of Multidrug Efflux Pump Inhibitors
title_sort microfluidic device for simple and rapid evaluation of multidrug efflux pump inhibitors
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3274760/
https://www.ncbi.nlm.nih.gov/pubmed/22347225
http://dx.doi.org/10.3389/fmicb.2012.00040
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