Abstract
In recent decades, invasive fungal infections have been increasing significantly, contributing to high incidences and mortality in immunosuppressed patients. Candida albicans (C. albicans) is the most prevalent opportunistic fungal pathogen in humans that can cause severe and often fatal bloodstream infections. Current antifungal agents have several limitations, including that only a small number of classes of antifungals are available, certain of which have severe toxicity and high cost. Moreover, the emergence of drug resistance is a new limitation to successful patient outcomes. Therefore, the development of antifungals with novel targets is an essential strategy for the efficient management of C. albicans infections. It is widely recognized that ion homeostasis is crucial for all living cells. Many studies have identified that ion-signaling and transduction networks are central to fungal survival by regulating gene expression, morphological transition, host invasion, stress response, and drug resistance. Dysregulation of ion homeostasis rapidly mediates cell death, forming the mechanistic basis of a growing number of compounds that elicit antifungal activity. Most of the potent antifungals have been widely used in the clinic, and certain of them have low toxicity, meaning that they may be expected to be used as antifungal drugs in the future. Hence, we briefly summarize the homeostasis regulation of several important ions, potential antifungal targets based on these ion-signaling networks, and antifungal compounds based on the disruption of ion homeostasis. This summary will help in designing effective drugs and identifying new targets for combating fungal diseases.
Highlights
Invasive fungal infections are on the rise around the world, in parallel with increasing populations of immunosuppressed individuals; overprescription of chemotherapeutics, antifungal agents, and steroids; and extensive use of catheters, as well as other medical implants (Tobudic et al, 2012)
We primarily review the genes, proteins, and enzymes involved in the regulation of ion homeostasis, including hydrogen (H+), calcium (Ca2+), iron (Fe3+), zinc (Zn2+), potassium (K+), and sodium (Na+) in C. albicans
The pH gradient created by V-ATPase is required for the secretion of numerous virulence-related proteins, such as aspartyl proteases, lipases, adhesions, and invasins, in the secretory pathway, which assists C. albicans in the invasion and colonization to host cells (Zhang and Rao, 2012)
Summary
Specialty section: This article was submitted to Fungal Pathogenesis, a section of the journal Frontiers in Cellular and Infection. Targets Against Candida albicans Based on Ion Homeostasis. Many studies have identified that ion-signaling and transduction networks are central to fungal survival by regulating gene expression, morphological transition, host invasion, stress response, and drug resistance. Dysregulation of ion homeostasis rapidly mediates cell death, forming the mechanistic basis of a growing number of compounds that elicit antifungal activity. We briefly summarize the homeostasis regulation of several important ions, potential antifungal targets based on these ion-signaling networks, and antifungal compounds based on the disruption of ion homeostasis. This summary will help in designing effective drugs and identifying new targets for combating fungal diseases
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