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dc.contributor.authorIyer, Kali R.en_US
dc.contributor.authorCamara, Kaddyen_US
dc.contributor.authorDaniel-Ivad, Martinen_US
dc.contributor.authorTrilles, Richarden_US
dc.contributor.authorPimentel-Elardo, Sheila M.en_US
dc.contributor.authorFossen, Jen L.en_US
dc.contributor.authorMarchillo, Karenen_US
dc.contributor.authorLiu, Zhongleen_US
dc.contributor.authorSingh, Shaktien_US
dc.contributor.authorMuñoz, José F.en_US
dc.contributor.authorKim, Sang Huen_US
dc.contributor.authorPorco, John A.en_US
dc.contributor.authorCuomo, Christina A.en_US
dc.contributor.authorWilliams, Noelle S.en_US
dc.contributor.authorIbrahim, Ashraf S.en_US
dc.contributor.authorEdwards, John E.en_US
dc.contributor.authorAndes, David R.en_US
dc.contributor.authorNodwell, Justin R.en_US
dc.contributor.authorBrown, Lauren E.en_US
dc.contributor.authorWhitesell, Lukeen_US
dc.contributor.authorRobbins, Nicoleen_US
dc.contributor.authorCowen, Leah E.en_US
dc.coverage.spatialEnglanden_US
dc.date2020-11-12
dc.date.accessioned2021-04-07T13:55:35Z
dc.date.available2021-04-07T13:55:35Z
dc.date.issued2020-12-22
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/33353950
dc.identifier.citationKali R Iyer, Kaddy Camara, Martin Daniel-Ivad, Richard Trilles, Sheila M Pimentel-Elardo, Jen L Fossen, Karen Marchillo, Zhongle Liu, Shakti Singh, José F Muñoz, Sang Hu Kim, John A Porco, Christina A Cuomo, Noelle S Williams, Ashraf S Ibrahim, John E Edwards, David R Andes, Justin R Nodwell, Lauren E Brown, Luke Whitesell, Nicole Robbins, Leah E Cowen. 2020. "An oxindole efflux inhibitor potentiates azoles and impairs virulence in the fungal pathogen Candida auris.." Nat Commun, Volume 11, Issue 1, pp. 6429 - ?. https://doi.org/10.1038/s41467-020-20183-3
dc.identifier.issn2041-1723
dc.identifier.urihttps://hdl.handle.net/2144/42361
dc.description.abstractCandida auris is an emerging fungal pathogen that exhibits resistance to multiple drugs, including the most commonly prescribed antifungal, fluconazole. Here, we use a combinatorial screening approach to identify a bis-benzodioxolylindolinone (azoffluxin) that synergizes with fluconazole against C. auris. Azoffluxin enhances fluconazole activity through the inhibition of efflux pump Cdr1, thus increasing intracellular fluconazole levels. This activity is conserved across most C. auris clades, with the exception of clade III. Azoffluxin also inhibits efflux in highly azole-resistant strains of Candida albicans, another human fungal pathogen, increasing their susceptibility to fluconazole. Furthermore, azoffluxin enhances fluconazole activity in mice infected with C. auris, reducing fungal burden. Our findings suggest that pharmacologically targeting Cdr1 in combination with azoles may be an effective strategy to control infection caused by azole-resistant isolates of C. auris.en_US
dc.description.sponsorshipU01 TR002625 - NCATS NIH HHS; MOP-133636 - CIHR; U19 AI110818 - NIAID NIH HHS; R35 GM118173 - NIGMS NIH HHS; FDN-154288 - CIHR; R01 AI141202 - NIAID NIH HHS; R01 AI073289 - NIAID NIH HHSen_US
dc.format.extentp. 6429en_US
dc.languageeng
dc.language.isoen_US
dc.relation.ispartofNat Commun
dc.rights© The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/.
dc.subjectAnimalsen_US
dc.subjectAntifungal agentsen_US
dc.subjectAzolesen_US
dc.subjectCandidaen_US
dc.subjectDrug evaluation, preclinicalen_US
dc.subjectDrug synergismen_US
dc.subjectFluconazoleen_US
dc.subjectFungal proteinsen_US
dc.subjectGene deletionen_US
dc.subjectHumansen_US
dc.subjectMiceen_US
dc.subjectOxindolesen_US
dc.subjectVirulenceen_US
dc.titleAn oxindole efflux inhibitor potentiates azoles and impairs virulence in the fungal pathogen Candida aurisen_US
dc.typeArticleen_US
dc.description.versionPublished versionen_US
dc.identifier.doi10.1038/s41467-020-20183-3
pubs.elements-sourcepubmeden_US
pubs.notesEmbargo: Not knownen_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, College of Arts & Sciencesen_US
pubs.organisational-groupBoston University, College of Arts & Sciences, Department of Chemistryen_US
pubs.publication-statusPublished onlineen_US
dc.identifier.orcid0000-0001-9489-484X (Brown, Lauren E)
dc.identifier.mycv583984


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© The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Except where otherwise noted, this item's license is described as © The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.