Zinc and Iron Homeostasis: Target-Based Drug Screening as New Route for Antifungal Drug Development

Research output: Contribution to journalArticlepeer-review

Standard

Harvard

APA

Vancouver

Author

Bibtex

@article{62c96620e32f4461b549621bc9134157,
title = "Zinc and Iron Homeostasis: Target-Based Drug Screening as New Route for Antifungal Drug Development",
abstract = "The incidence of fungal diseases is on the rise and the number of fatalities is still unacceptably high. While advances into antifungal drug development have been made there remains an urgent need to develop novel antifungal agents targeting as-yet unexploited pathways, such as metal ion homeostasis. Here we report such an approach by developing a metal sensor screen in the opportunistic human fungal pathogen Candida albicans. Using this reporter strain, we screened a library of 1,200 compounds and discovered several active compounds not previously described as chemical entities with antifungal properties. Two of these, artemisinin and pyrvinium pamoate, have been further characterized and their interference with metal homeostasis and potential as novel antifungal compounds validated. Lastly, we demonstrate that the same strain can be used to report on intracellular conditions within host phagocytes, paving the way toward the development of novel screening platforms that could identify compounds with the potential to perturb ion homeostasis of the pathogen specifically within host cells.",
keywords = "Candida, antifungals, artemisinin, high throughput drug screening, iron homeostasis, pyrvinium pamoate, zinc homeostasis",
author = "Claudia Simm and May, {Robin C}",
year = "2019",
month = may,
day = "29",
doi = "10.3389/fcimb.2019.00181",
language = "English",
volume = "9",
journal = "Frontiers in cellular and infection microbiology",
issn = "2235-2988",
publisher = "Frontiers Media S.A.",

}

RIS

TY - JOUR

T1 - Zinc and Iron Homeostasis

T2 - Target-Based Drug Screening as New Route for Antifungal Drug Development

AU - Simm, Claudia

AU - May, Robin C

PY - 2019/5/29

Y1 - 2019/5/29

N2 - The incidence of fungal diseases is on the rise and the number of fatalities is still unacceptably high. While advances into antifungal drug development have been made there remains an urgent need to develop novel antifungal agents targeting as-yet unexploited pathways, such as metal ion homeostasis. Here we report such an approach by developing a metal sensor screen in the opportunistic human fungal pathogen Candida albicans. Using this reporter strain, we screened a library of 1,200 compounds and discovered several active compounds not previously described as chemical entities with antifungal properties. Two of these, artemisinin and pyrvinium pamoate, have been further characterized and their interference with metal homeostasis and potential as novel antifungal compounds validated. Lastly, we demonstrate that the same strain can be used to report on intracellular conditions within host phagocytes, paving the way toward the development of novel screening platforms that could identify compounds with the potential to perturb ion homeostasis of the pathogen specifically within host cells.

AB - The incidence of fungal diseases is on the rise and the number of fatalities is still unacceptably high. While advances into antifungal drug development have been made there remains an urgent need to develop novel antifungal agents targeting as-yet unexploited pathways, such as metal ion homeostasis. Here we report such an approach by developing a metal sensor screen in the opportunistic human fungal pathogen Candida albicans. Using this reporter strain, we screened a library of 1,200 compounds and discovered several active compounds not previously described as chemical entities with antifungal properties. Two of these, artemisinin and pyrvinium pamoate, have been further characterized and their interference with metal homeostasis and potential as novel antifungal compounds validated. Lastly, we demonstrate that the same strain can be used to report on intracellular conditions within host phagocytes, paving the way toward the development of novel screening platforms that could identify compounds with the potential to perturb ion homeostasis of the pathogen specifically within host cells.

KW - Candida

KW - antifungals

KW - artemisinin

KW - high throughput drug screening

KW - iron homeostasis

KW - pyrvinium pamoate

KW - zinc homeostasis

U2 - 10.3389/fcimb.2019.00181

DO - 10.3389/fcimb.2019.00181

M3 - Article

C2 - 31192169

VL - 9

JO - Frontiers in cellular and infection microbiology

JF - Frontiers in cellular and infection microbiology

SN - 2235-2988

M1 - 181

ER -