Identified Seaweed Compound Diphenylmethane Serves as an Efflux Pump Inhibitor in Drug-Resistant <i>Escherichia coli</i>

Drug efflux pumps are one of the major elements used by antibiotic-resistant bacteria. Efflux pump inhibitors (EPIs) are potential therapeutic agents for adjunctive therapy, which can restore the activity of antibiotics that are no longer effective against pathogens. This study evaluated the seaweed...

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Autores principales:	Wen-Jung Lu, Pang-Hung Hsu, Chun-Ju Chang, Cheng-Kuan Su, Yan-Jyun Huang, Hsuan-Ju Lin, Margaret Lai, Gui-Xia Ooi, Jing-Yi Dai, Hong-Ting Victor Lin
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	seaweeds efflux pump inhibitors multidrug resistance drug transporters diphenylmethane aromatic compounds Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/8cb407740c8245b9bae60db66a861784
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spelling	oai:doaj.org-article:8cb407740c8245b9bae60db66a8617842021-11-25T16:24:20ZIdentified Seaweed Compound Diphenylmethane Serves as an Efflux Pump Inhibitor in Drug-Resistant <i>Escherichia coli</i>10.3390/antibiotics101113782079-6382https://doaj.org/article/8cb407740c8245b9bae60db66a8617842021-11-01T00:00:00Zhttps://www.mdpi.com/2079-6382/10/11/1378https://doaj.org/toc/2079-6382Drug efflux pumps are one of the major elements used by antibiotic-resistant bacteria. Efflux pump inhibitors (EPIs) are potential therapeutic agents for adjunctive therapy, which can restore the activity of antibiotics that are no longer effective against pathogens. This study evaluated the seaweed compound diphenylmethane (DPM) for its EPI activity. The IC<sub>50</sub> and modulation results showed that DPM has no antibacterial activity but can potentiate the activity of antibiotics against drug-resistant <i>E. coli</i>. Time-kill studies reported that a combination of DPM and erythromycin exhibited greater inhibitory activity against drug-resistant <i>Escherichia coli</i>. Dye accumulation and dye efflux studies using Hoechst 33342 and ethidium bromide showed that the addition of DPM significantly increased dye accumulation and reduced dye efflux in drug-resistant <i>E. coli</i>, suggesting its interference with dye translocation by an efflux pump. Using MALDI-TOF, it was observed that the addition of DPM could continuously reduce antibiotic efflux in drug-resistant <i>E. coli</i>. Additionally, DPM did not seem to damage the <i>E. coli</i> membranes, and the cell toxicity test showed that it features mild human-cell toxicity. In conclusion, these findings showed that DPM could serve as a potential EPI for drug-resistant <i>E. coli</i>.Wen-Jung LuPang-Hung HsuChun-Ju ChangCheng-Kuan SuYan-Jyun HuangHsuan-Ju LinMargaret LaiGui-Xia OoiJing-Yi DaiHong-Ting Victor LinMDPI AGarticleseaweedsefflux pump inhibitorsmultidrug resistancedrug transportersdiphenylmethanearomatic compoundsTherapeutics. PharmacologyRM1-950ENAntibiotics, Vol 10, Iss 1378, p 1378 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	seaweeds efflux pump inhibitors multidrug resistance drug transporters diphenylmethane aromatic compounds Therapeutics. Pharmacology RM1-950
spellingShingle	seaweeds efflux pump inhibitors multidrug resistance drug transporters diphenylmethane aromatic compounds Therapeutics. Pharmacology RM1-950 Wen-Jung Lu Pang-Hung Hsu Chun-Ju Chang Cheng-Kuan Su Yan-Jyun Huang Hsuan-Ju Lin Margaret Lai Gui-Xia Ooi Jing-Yi Dai Hong-Ting Victor Lin Identified Seaweed Compound Diphenylmethane Serves as an Efflux Pump Inhibitor in Drug-Resistant <i>Escherichia coli</i>
description	Drug efflux pumps are one of the major elements used by antibiotic-resistant bacteria. Efflux pump inhibitors (EPIs) are potential therapeutic agents for adjunctive therapy, which can restore the activity of antibiotics that are no longer effective against pathogens. This study evaluated the seaweed compound diphenylmethane (DPM) for its EPI activity. The IC<sub>50</sub> and modulation results showed that DPM has no antibacterial activity but can potentiate the activity of antibiotics against drug-resistant <i>E. coli</i>. Time-kill studies reported that a combination of DPM and erythromycin exhibited greater inhibitory activity against drug-resistant <i>Escherichia coli</i>. Dye accumulation and dye efflux studies using Hoechst 33342 and ethidium bromide showed that the addition of DPM significantly increased dye accumulation and reduced dye efflux in drug-resistant <i>E. coli</i>, suggesting its interference with dye translocation by an efflux pump. Using MALDI-TOF, it was observed that the addition of DPM could continuously reduce antibiotic efflux in drug-resistant <i>E. coli</i>. Additionally, DPM did not seem to damage the <i>E. coli</i> membranes, and the cell toxicity test showed that it features mild human-cell toxicity. In conclusion, these findings showed that DPM could serve as a potential EPI for drug-resistant <i>E. coli</i>.
format	article
author	Wen-Jung Lu Pang-Hung Hsu Chun-Ju Chang Cheng-Kuan Su Yan-Jyun Huang Hsuan-Ju Lin Margaret Lai Gui-Xia Ooi Jing-Yi Dai Hong-Ting Victor Lin
author_facet	Wen-Jung Lu Pang-Hung Hsu Chun-Ju Chang Cheng-Kuan Su Yan-Jyun Huang Hsuan-Ju Lin Margaret Lai Gui-Xia Ooi Jing-Yi Dai Hong-Ting Victor Lin
author_sort	Wen-Jung Lu
title	Identified Seaweed Compound Diphenylmethane Serves as an Efflux Pump Inhibitor in Drug-Resistant <i>Escherichia coli</i>
title_short	Identified Seaweed Compound Diphenylmethane Serves as an Efflux Pump Inhibitor in Drug-Resistant <i>Escherichia coli</i>
title_full	Identified Seaweed Compound Diphenylmethane Serves as an Efflux Pump Inhibitor in Drug-Resistant <i>Escherichia coli</i>
title_fullStr	Identified Seaweed Compound Diphenylmethane Serves as an Efflux Pump Inhibitor in Drug-Resistant <i>Escherichia coli</i>
title_full_unstemmed	Identified Seaweed Compound Diphenylmethane Serves as an Efflux Pump Inhibitor in Drug-Resistant <i>Escherichia coli</i>
title_sort	identified seaweed compound diphenylmethane serves as an efflux pump inhibitor in drug-resistant <i>escherichia coli</i>
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/8cb407740c8245b9bae60db66a861784
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Identified Seaweed Compound Diphenylmethane Serves as an Efflux Pump Inhibitor in Drug-Resistant <i>Escherichia coli</i>

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