Small molecule inhibitors of the Candida albicans budded-to-hyphal transition act through multiple signaling pathways.

The ability of the pathogenic yeast Candida albicans to interconvert between budded and hyphal growth states, herein termed the budded-to-hyphal transition (BHT), is important for C. albicans development and virulence. The BHT is under the control of multiple cell signaling pathways that respond to...

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Autores principales:	John Midkiff, Nathan Borochoff-Porte, Dylan White, Douglas I Johnson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/55cf065d59224d31a55fc914f899af2a
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spelling	oai:doaj.org-article:55cf065d59224d31a55fc914f899af2a2021-11-04T06:07:47ZSmall molecule inhibitors of the Candida albicans budded-to-hyphal transition act through multiple signaling pathways.1932-620310.1371/journal.pone.0025395https://doaj.org/article/55cf065d59224d31a55fc914f899af2a2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21966518/?tool=EBIhttps://doaj.org/toc/1932-6203The ability of the pathogenic yeast Candida albicans to interconvert between budded and hyphal growth states, herein termed the budded-to-hyphal transition (BHT), is important for C. albicans development and virulence. The BHT is under the control of multiple cell signaling pathways that respond to external stimuli, including nutrient availability, high temperature, and pH. Previous studies identified 21 small molecules that could inhibit the C. albicans BHT in response to carbon limitation in Spider media. However, the studies herein show that the BHT inhibitors had varying efficacies in other hyphal-inducing media, reflecting their varying abilities to block signaling pathways associated with the different media. Chemical epistasis analyses suggest that most, but not all, of the BHT inhibitors were acting through either the Efg1 or Cph1 signaling pathways. Notably, the BHT inhibitor clozapine, a FDA-approved drug used to treat atypical schizophrenia by inhibiting G-protein-coupled dopamine receptors in the brain, and several of its functional analogs were shown to act at the level of the Gpr1 G-protein-coupled receptor. These studies are the first step in determining the target and mechanism of action of these BHT inhibitors, which may have therapeutic anti-fungal utility in the future.John MidkiffNathan Borochoff-PorteDylan WhiteDouglas I JohnsonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 9, p e25395 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q John Midkiff Nathan Borochoff-Porte Dylan White Douglas I Johnson Small molecule inhibitors of the Candida albicans budded-to-hyphal transition act through multiple signaling pathways.
description	The ability of the pathogenic yeast Candida albicans to interconvert between budded and hyphal growth states, herein termed the budded-to-hyphal transition (BHT), is important for C. albicans development and virulence. The BHT is under the control of multiple cell signaling pathways that respond to external stimuli, including nutrient availability, high temperature, and pH. Previous studies identified 21 small molecules that could inhibit the C. albicans BHT in response to carbon limitation in Spider media. However, the studies herein show that the BHT inhibitors had varying efficacies in other hyphal-inducing media, reflecting their varying abilities to block signaling pathways associated with the different media. Chemical epistasis analyses suggest that most, but not all, of the BHT inhibitors were acting through either the Efg1 or Cph1 signaling pathways. Notably, the BHT inhibitor clozapine, a FDA-approved drug used to treat atypical schizophrenia by inhibiting G-protein-coupled dopamine receptors in the brain, and several of its functional analogs were shown to act at the level of the Gpr1 G-protein-coupled receptor. These studies are the first step in determining the target and mechanism of action of these BHT inhibitors, which may have therapeutic anti-fungal utility in the future.
format	article
author	John Midkiff Nathan Borochoff-Porte Dylan White Douglas I Johnson
author_facet	John Midkiff Nathan Borochoff-Porte Dylan White Douglas I Johnson
author_sort	John Midkiff
title	Small molecule inhibitors of the Candida albicans budded-to-hyphal transition act through multiple signaling pathways.
title_short	Small molecule inhibitors of the Candida albicans budded-to-hyphal transition act through multiple signaling pathways.
title_full	Small molecule inhibitors of the Candida albicans budded-to-hyphal transition act through multiple signaling pathways.
title_fullStr	Small molecule inhibitors of the Candida albicans budded-to-hyphal transition act through multiple signaling pathways.
title_full_unstemmed	Small molecule inhibitors of the Candida albicans budded-to-hyphal transition act through multiple signaling pathways.
title_sort	small molecule inhibitors of the candida albicans budded-to-hyphal transition act through multiple signaling pathways.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/55cf065d59224d31a55fc914f899af2a
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Small molecule inhibitors of the Candida albicans budded-to-hyphal transition act through multiple signaling pathways.

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