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Article: Imidazole Type Antifungal Drugs Are Effective Colistin Adjuvants That Resensitize Colistin‐Resistant Enterobacteriaceae

TitleImidazole Type Antifungal Drugs Are Effective Colistin Adjuvants That Resensitize Colistin‐Resistant Enterobacteriaceae
Authors
Keywordscolistin adjuvants
drug repurposing
econazole
enterobacteriaceae
membrane potentials
Issue Date2020
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2366-3987
Citation
Advanced Therapeutics, 2020, Epub 2020-06-22, p. article no. 2000084 How to Cite?
AbstractThe clinical value of the last‐line antibiotic colistin is limited by its toxicity and the increasing prevalence of drug resistance in recent years. These two issues can be tackled by searching for adjuvant compounds that enhance colistin activity and facilitate reduction of treatment dosage. This study identifies a Food and Drug Administration (FDA)‐approved drug, econazole, which can act synergistically with colistin to effectively eradicate colistin‐resistant bacteria both in vitro and in a mouse infection model, and treat infections caused by colistin‐susceptible bacteria in lower doses. Structural analysis shows that econazole exhibits high lipid affinity and acts as an ionophore. Functional assays and microscopy analysis confirm that econazole causes dissipation of transmembrane proton motive force (PMF) and damage to the bacterial cell membrane. Its synergistic effect with colistin might be due to the combination of these two compounds causing further collapse of PMF, arrest of various cellular functions, and eventually cell death. These findings suggest that the econazole and colistin drug combination is highly effective in eradicating colistin‐resistant Gram negative bacterial pathogens regardless of their mechanism of colistin resistance.
Persistent Identifierhttp://hdl.handle.net/10722/284533
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorXu, C-
dc.contributor.authorChen, K-
dc.contributor.authorChan, KF-
dc.contributor.authorChan, EWC-
dc.contributor.authorGuo, X-
dc.contributor.authorChow, HY-
dc.contributor.authorZhao, G-
dc.contributor.authorZeng, P-
dc.contributor.authorWang, M-
dc.contributor.authorZhu, Y-
dc.contributor.authorLi, X-
dc.contributor.authorWong, KY-
dc.contributor.authorChen, S-
dc.date.accessioned2020-08-07T08:59:00Z-
dc.date.available2020-08-07T08:59:00Z-
dc.date.issued2020-
dc.identifier.citationAdvanced Therapeutics, 2020, Epub 2020-06-22, p. article no. 2000084-
dc.identifier.urihttp://hdl.handle.net/10722/284533-
dc.description.abstractThe clinical value of the last‐line antibiotic colistin is limited by its toxicity and the increasing prevalence of drug resistance in recent years. These two issues can be tackled by searching for adjuvant compounds that enhance colistin activity and facilitate reduction of treatment dosage. This study identifies a Food and Drug Administration (FDA)‐approved drug, econazole, which can act synergistically with colistin to effectively eradicate colistin‐resistant bacteria both in vitro and in a mouse infection model, and treat infections caused by colistin‐susceptible bacteria in lower doses. Structural analysis shows that econazole exhibits high lipid affinity and acts as an ionophore. Functional assays and microscopy analysis confirm that econazole causes dissipation of transmembrane proton motive force (PMF) and damage to the bacterial cell membrane. Its synergistic effect with colistin might be due to the combination of these two compounds causing further collapse of PMF, arrest of various cellular functions, and eventually cell death. These findings suggest that the econazole and colistin drug combination is highly effective in eradicating colistin‐resistant Gram negative bacterial pathogens regardless of their mechanism of colistin resistance.-
dc.languageeng-
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2366-3987-
dc.relation.ispartofAdvanced Therapeutics-
dc.rightsPreprint This is the pre-peer reviewed version of the following article: [FULL CITE], which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Postprint This is the peer reviewed version of the following article: [FULL CITE], which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.-
dc.subjectcolistin adjuvants-
dc.subjectdrug repurposing-
dc.subjecteconazole-
dc.subjectenterobacteriaceae-
dc.subjectmembrane potentials-
dc.titleImidazole Type Antifungal Drugs Are Effective Colistin Adjuvants That Resensitize Colistin‐Resistant Enterobacteriaceae-
dc.typeArticle-
dc.identifier.emailChow, HY: hchowhy@connect.hku.hk-
dc.identifier.emailLi, X: xuechenl@hku.hk-
dc.identifier.authorityLi, X=rp00742-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/adtp.202000084-
dc.identifier.scopuseid_2-s2.0-85103744538-
dc.identifier.hkuros311898-
dc.identifier.volumeEpub 2020-06-22-
dc.identifier.spagearticle no. 2000084-
dc.identifier.epagearticle no. 2000084-
dc.identifier.eissn2366-3987-
dc.identifier.isiWOS:000543544900001-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl2366-3987-

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