Chemical inhibitors of Candida albicans hyphal morphogenesis target endocytosis

Hagit Bar-Yosef, Nora Vivanco Gonzalez, Shay Ben-Aroya, Stephen J. Kron, Daniel Kornitzer

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number5692
JournalScientific Reports
Volume7
Issue number1
Early online date18 Jul 2017
DOIs
StatePublished - 1 Dec 2017

All Science Journal Classification (ASJC) codes

  • General

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