More than flipping the lid: Cdc50 contributes to echinocandin resistance by regulating calcium homeostasis in Cryptococcus neoformans
Authors:Chengjun Cao1 and Chaoyang Xue1,2
doi: 10.15698/mic2020.04.714
Volume 7, pp. 115 to 118, published 20/02/2020.
1 Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ USA.
2 Department of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School, Rutgers University, Newark, NJ USA.
Keywords:
calcium/calcineurin signaling, lipid flippase, Cryptococcus neoformans, antifungal drug resistance
Corresponding Author(s):
Conflict of interest statement:
Authors declare there is no competing financial or other interests that might influence the matters discussed in this article.
Please cite this article as:
Chengjun Cao and Chaoyang Xue (2020). More than flipping the lid: Cdc50 contributes to echinocandin resistance by regulating calcium homeostasis in Cryptococcus neoformans. Microbial Cell 7(4): 115-118. doi: 10.15698/mic2020.04.714
© 2020 Cao and Xue. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Echinocandins are the newest fungicidal drug class approved for clinical use against common invasive mycoses. Yet, they are ineffective against cryptococcosis, predominantly caused by Cryptococcus neoformans. The underlying mechanisms of innate echinocandin resistance in C. neoformans remain unclear. We know that Cdc50, the β-subunit of the lipid translocase (flippase), mediates echinocandin resistance, as loss of the CDC50 gene sensitizes C. neoformans to caspofungin, a member of the echinocandins class. We sought to elucidate how Cdc50 facilitates caspofungin resistance by performing a forward genetic screen for cdc50Δ suppressor mutations that are caspofungin resistant. We identified a novel mechanosensitive calcium channel protein Crm1 that correlates with Cdc50 function (Cao et al., 2019). In addition to regulating phospholipid translocation, Cdc50 also interacts with Crm1 to regulate intracellular calcium homeostasis and calcium/calcineurin signaling that likely drives caspofungin resistance in C. neoformans. Our study revealed a novel dual function of Cdc50 that connects lipid flippase with calcium signaling. These unexpected findings provide new insights into the mechanisms of echinocandin resistance in C. neoformans that may drive future drug design.