Abstract
Fungal infections are a growing public health concern, and an increasingly important cause of human mortality, with Candida species being amongst the most frequently encountered of these opportunistic fungal pathogens. Several Candida species are polymorphic, and able to transition between distinct morphological states, including yeast, hyphal, and pseudohyphal forms. While not all Candida pathogens are polymorphic, the ability to undergo morphogenesis is linked with the virulence of many of these pathogens. There are also many connections between Candida morphogenesis and antifungal drug treatment and susceptibility. Here, we review how Candida morphogenesis—a key virulence trait—is linked with antifungal drugs and antifungal drug resistance. We highlight how antifungal therapeutics are able to modulate morphogenesis in both sensitive and drug-resistant Candida strains, the shared signaling pathways that mediate both morphogenesis and the cellular response to antifungal drugs and drug resistance, and the connection between Candida morphology, drug resistance, and biofilm growth. We further review the development of anti-virulence drugs, and targeting Candida morphogenesis as a novel therapeutic strategy to target fungal pathogens. Together, this review highlights important connections between fungal morphogenesis, virulence, and susceptibility to antifungals.
Highlights
Introduction to Candida and Candidiasis InfectionsThe fungal kingdom contains diverse organisms which make significant contributions to supporting life on our planet
We further review the development of anti-virulence drugs, and targeting Candida morphogenesis as a novel therapeutic strategy to target fungal pathogens
While deleting genes involved in morphogenesis often results in loss of virulence, there are factors that are involved in morphogenesis and not virulence, and, virulence factors that play no apparent role in morphogenesis [54]
Summary
The fungal kingdom contains diverse organisms which make significant contributions to supporting life on our planet. C. auris has recently emerged as a highly multidrug-resistant pathogen, and a serious global health threat [32] Amongst these Candida pathogens, C. albicans is the species mostly common associated with human infection [14]. Each of these Candida species possess critical factors that contribute to these fungi being well adapted as a pathogen to the human host Processes such as cellular morphogenesis, cell-surface adhesion, phenotypic switching, biofilm formation, antifungal drug resistance, and secretion of hydrolytic enzymes are all well-established virulence mechanisms that aid in the success of these species as pathogens [33,34,35,36,37,38,39,40]
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