Non- albicans Candida Species: Immune Response, Evasion Mechanisms, and New Plant-Derived Alternative Therapies

Abstract

Fungal infections caused by Candida species have become a constant threat to public health, especially for immunocompromised patients, who are considered susceptible to this type of opportunistic infections. Candida albicans is known as the most common etiological agent of candidiasis; however, other species, such as Candida tropicalis, Candida parapsilosis, Nakaseomyces glabrata (previously known as Candida glabrata), Candida auris, Candida guilliermondii, and Pichia kudriavzevii (previously named as Candida krusei), have also gained great importance in recent years. The increasing frequency of the isolation of this non-albicans Candida species is associated with different factors, such as constant exposure to antifungal drugs, the use of catheters in hospitalized patients, cancer, age, and geographic distribution. The main concerns for the control of these pathogens include their ability to evade the mechanisms of action of different drugs, thus developing resistance to antifungal drugs, and it has also been shown that some of these species also manage to evade the host's immunity. These biological traits make candidiasis treatment a challenging task. In this review manuscript, a detailed update of the recent literature on the six most relevant non-albicans Candida species is provided, focusing on the immune response, evasion mechanisms, and new plant-derived compounds with antifungal properties.

Keywords: antifungal drugs; antifungal immunity; candidiasis; host–fungus interaction; innate immune sensing.

Figure 1

Antifungal resistance mechanisms in non-albicans Candida species. (A) Mutation in ergosterol biosynthesis that causes a decrease in the ergosterol content in the cell membrane and induces the replacement of biosynthetic precursors such as liquesterol and lanosterol. (B) Mutation in ERG11 that encodes the enzyme lanosterol 14α-demethylase, causing defects in ergosterol synthesis. (C) Mutation in cytosine deaminase (FCY1), cytosine permease (FCY2) and uracil phosphoribosyltransferase (FUR1) facilitating resistance to flucytosine. (D) Mutation in FKS1 that generates resistance to caspofungins.