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Screening the CALIBR ReFRAME Library in Search for Inhibitors of Candida auris Biofilm Formation

Candida auris is an emerging yeast which, since its first isolation about a decade ago, has spread rapidly and triggered major infectious outbreaks in health care facilities around the world. C. auris strains often display resistance to clinically-used antifungal agents, contributing to high mortali...

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Autores principales: Wall, Gina, Chen, Emily, Hull, Mitchell V., Lopez-Ribot, Jose L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723901/
https://www.ncbi.nlm.nih.gov/pubmed/33324579
http://dx.doi.org/10.3389/fcimb.2020.597931
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author Wall, Gina
Chen, Emily
Hull, Mitchell V.
Lopez-Ribot, Jose L.
author_facet Wall, Gina
Chen, Emily
Hull, Mitchell V.
Lopez-Ribot, Jose L.
author_sort Wall, Gina
collection PubMed
description Candida auris is an emerging yeast which, since its first isolation about a decade ago, has spread rapidly and triggered major infectious outbreaks in health care facilities around the world. C. auris strains often display resistance to clinically-used antifungal agents, contributing to high mortality rates. Thus, there is an urgent need for new antifungals to contain the spread of this emerging multi-drug resistant pathogen and to improve patient outcomes. However, the timeline for the development of a new antifungal agent typically exceeds 10‑15 years. Thus, repurposing of current drugs could significantly accelerate the development and eventual deployment of novel therapies for the treatment of C. auris infections. Toward this end, in this study we have profiled a library of known drugs encompassing approximately 12,000 clinical-stage or FDA-approved small molecules in search for known molecules with antifungal activity against C. auris; more specifically, those capable of inhibiting C. auris biofilm formation. From this library, 100 compounds displaying antifungal activity were identified in the initial screen, including 26 compounds for which a dose-response relationship with biofilm-inhibitory activity against C. auris could be confirmed. Of these, five were identified as the most interesting potential repositionable candidates. Due to their known pharmacological and human safety profiles, identification of such compounds should allow for their accelerated preclinical and clinical development for the treatment of C. auris infections.
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spelling pubmed-77239012020-12-14 Screening the CALIBR ReFRAME Library in Search for Inhibitors of Candida auris Biofilm Formation Wall, Gina Chen, Emily Hull, Mitchell V. Lopez-Ribot, Jose L. Front Cell Infect Microbiol Cellular and Infection Microbiology Candida auris is an emerging yeast which, since its first isolation about a decade ago, has spread rapidly and triggered major infectious outbreaks in health care facilities around the world. C. auris strains often display resistance to clinically-used antifungal agents, contributing to high mortality rates. Thus, there is an urgent need for new antifungals to contain the spread of this emerging multi-drug resistant pathogen and to improve patient outcomes. However, the timeline for the development of a new antifungal agent typically exceeds 10‑15 years. Thus, repurposing of current drugs could significantly accelerate the development and eventual deployment of novel therapies for the treatment of C. auris infections. Toward this end, in this study we have profiled a library of known drugs encompassing approximately 12,000 clinical-stage or FDA-approved small molecules in search for known molecules with antifungal activity against C. auris; more specifically, those capable of inhibiting C. auris biofilm formation. From this library, 100 compounds displaying antifungal activity were identified in the initial screen, including 26 compounds for which a dose-response relationship with biofilm-inhibitory activity against C. auris could be confirmed. Of these, five were identified as the most interesting potential repositionable candidates. Due to their known pharmacological and human safety profiles, identification of such compounds should allow for their accelerated preclinical and clinical development for the treatment of C. auris infections. Frontiers Media S.A. 2020-11-25 /pmc/articles/PMC7723901/ /pubmed/33324579 http://dx.doi.org/10.3389/fcimb.2020.597931 Text en Copyright © 2020 Wall, Chen, Hull and Lopez-Ribot http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Wall, Gina
Chen, Emily
Hull, Mitchell V.
Lopez-Ribot, Jose L.
Screening the CALIBR ReFRAME Library in Search for Inhibitors of Candida auris Biofilm Formation
title Screening the CALIBR ReFRAME Library in Search for Inhibitors of Candida auris Biofilm Formation
title_full Screening the CALIBR ReFRAME Library in Search for Inhibitors of Candida auris Biofilm Formation
title_fullStr Screening the CALIBR ReFRAME Library in Search for Inhibitors of Candida auris Biofilm Formation
title_full_unstemmed Screening the CALIBR ReFRAME Library in Search for Inhibitors of Candida auris Biofilm Formation
title_short Screening the CALIBR ReFRAME Library in Search for Inhibitors of Candida auris Biofilm Formation
title_sort screening the calibr reframe library in search for inhibitors of candida auris biofilm formation
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723901/
https://www.ncbi.nlm.nih.gov/pubmed/33324579
http://dx.doi.org/10.3389/fcimb.2020.597931
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