Original Research ARTICLE
Zinc and Iron homeostasis: Target-based drug screening as new route for antifungal drug development.
- 1Monash University, Australia
- 2University of Birmingham, United Kingdom
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 fatal human fungal pathogen Candida albicans. Using this reporter strain, we screened a library of 1200 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 characterised 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 towards 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, Antifungal, High throughput screening (HTS), Zinc homeostasis, iron homeostasis, Artemisinin, pyrvinium pamoate
Received: 13 Apr 2019;
Accepted: 13 May 2019.
Edited by:Jose L. Lopez-Ribot, University of Texas at San Antonio, United States
Reviewed by:Samuel Lee, Geisel School of Medicine, United States
Lawrence C. Myers, Geisel School of Medicine, Dartmouth College, United States
Copyright: © 2019 Simm and May. 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.
* Correspondence: Dr. Claudia Simm, Monash University, Melbourne, Australia, email@example.com