Chemical inhibitors of Candida albicans hyphal morphogenesis target endocytosis

Abstract Candida albicans is an opportunistic pathogen, typically found as a benign commensal yeast living on skin and mucosa, but poised to invade injured tissue to cause local infections. In debilitated and immunocompromised individuals, C. albicans may spread to cause life-threatening systemic in...

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Autores principales:	Hagit Bar-Yosef, Nora Vivanco Gonzalez, Shay Ben-Aroya, Stephen J. Kron, Daniel Kornitzer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4f5c25110a054679baebfc9be57e11a1
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spelling	oai:doaj.org-article:4f5c25110a054679baebfc9be57e11a12021-12-02T15:04:56ZChemical inhibitors of Candida albicans hyphal morphogenesis target endocytosis10.1038/s41598-017-05741-y2045-2322https://doaj.org/article/4f5c25110a054679baebfc9be57e11a12017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05741-yhttps://doaj.org/toc/2045-2322Abstract Candida albicans is an opportunistic pathogen, typically found as a benign commensal yeast living on skin and mucosa, but poised to invade injured tissue to cause local infections. In debilitated and immunocompromised individuals, C. albicans may spread to cause life-threatening systemic infections. Upon contact with serum and at body temperature, C. albicans performs a regulated switch to filamentous morphology, characterized by emergence of a germ tube from the yeast cell followed by mold-like growth of branching hyphae. The ability to switch between growth morphologies is an important virulence factor of C. albicans. To identify compounds able to inhibit hyphal morphogenesis, we screened libraries of existing drugs for inhibition of the hyphal switch under stringent conditions. Several compounds that specifically inhibited hyphal morphogenesis were identified. Chemogenomic analysis suggested an interaction with the endocytic pathway, which was confirmed by direct measurement of fluid-phase endocytosis in the presence of these compounds. These results suggest that the activity of the endocytic pathway, which is known to be particularly important for hyphal growth, represents an effective target for hyphae-inhibiting drugs.Hagit Bar-YosefNora Vivanco GonzalezShay Ben-AroyaStephen J. KronDaniel KornitzerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hagit Bar-Yosef Nora Vivanco Gonzalez Shay Ben-Aroya Stephen J. Kron Daniel Kornitzer Chemical inhibitors of Candida albicans hyphal morphogenesis target endocytosis
description	Abstract Candida albicans is an opportunistic pathogen, typically found as a benign commensal yeast living on skin and mucosa, but poised to invade injured tissue to cause local infections. In debilitated and immunocompromised individuals, C. albicans may spread to cause life-threatening systemic infections. Upon contact with serum and at body temperature, C. albicans performs a regulated switch to filamentous morphology, characterized by emergence of a germ tube from the yeast cell followed by mold-like growth of branching hyphae. The ability to switch between growth morphologies is an important virulence factor of C. albicans. To identify compounds able to inhibit hyphal morphogenesis, we screened libraries of existing drugs for inhibition of the hyphal switch under stringent conditions. Several compounds that specifically inhibited hyphal morphogenesis were identified. Chemogenomic analysis suggested an interaction with the endocytic pathway, which was confirmed by direct measurement of fluid-phase endocytosis in the presence of these compounds. These results suggest that the activity of the endocytic pathway, which is known to be particularly important for hyphal growth, represents an effective target for hyphae-inhibiting drugs.
format	article
author	Hagit Bar-Yosef Nora Vivanco Gonzalez Shay Ben-Aroya Stephen J. Kron Daniel Kornitzer
author_facet	Hagit Bar-Yosef Nora Vivanco Gonzalez Shay Ben-Aroya Stephen J. Kron Daniel Kornitzer
author_sort	Hagit Bar-Yosef
title	Chemical inhibitors of Candida albicans hyphal morphogenesis target endocytosis
title_short	Chemical inhibitors of Candida albicans hyphal morphogenesis target endocytosis
title_full	Chemical inhibitors of Candida albicans hyphal morphogenesis target endocytosis
title_fullStr	Chemical inhibitors of Candida albicans hyphal morphogenesis target endocytosis
title_full_unstemmed	Chemical inhibitors of Candida albicans hyphal morphogenesis target endocytosis
title_sort	chemical inhibitors of candida albicans hyphal morphogenesis target endocytosis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/4f5c25110a054679baebfc9be57e11a1
work_keys_str_mv	AT hagitbaryosef chemicalinhibitorsofcandidaalbicanshyphalmorphogenesistargetendocytosis AT noravivancogonzalez chemicalinhibitorsofcandidaalbicanshyphalmorphogenesistargetendocytosis AT shaybenaroya chemicalinhibitorsofcandidaalbicanshyphalmorphogenesistargetendocytosis AT stephenjkron chemicalinhibitorsofcandidaalbicanshyphalmorphogenesistargetendocytosis AT danielkornitzer chemicalinhibitorsofcandidaalbicanshyphalmorphogenesistargetendocytosis
_version_	1718388953255510016

Chemical inhibitors of Candida albicans hyphal morphogenesis target endocytosis

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