Abstract
The cell wall in Candida albicans is not only a tight protective envelope but also a point of contact with the human host that provides a dynamic response to the constantly changing environment in infection niches. Particularly important roles are attributed to proteins exposed at the fungal cell surface. These include proteins that are stably and covalently bound to the cell wall or cell membrane and those that are more loosely attached. Interestingly in this regard, numerous loosely attached proteins belong to the class of “moonlighting proteins” that are originally intracellular and that perform essentially different functions in addition to their primary housekeeping roles. These proteins also demonstrate unpredicted interactions with non-canonical partners at an a priori unexpected extracellular location, achieved via non-classical secretion routes. Acting both individually and collectively, the moonlighting proteins contribute to candidal virulence and pathogenicity through their involvement in mechanisms critical for successful host colonization and infection, such as the adhesion to host cells, interactions with plasma homeostatic proteolytic cascades, responses to stress conditions and molecular mimicry. The documented knowledge of the roles of these proteins in C. albicans pathogenicity has utility for assisting the design of new therapeutic, diagnostic and preventive strategies against candidiasis.
Highlights
Moonlighting Proteins—Definition and ClassificationProteins are multifunctional by nature
We critically summarize the current state of knowledge on cell surface-exposed moonlighting proteins in the opportunistic pathogen Candida albicans, one of the most common fungal pathogens in humans and in several other closely related and medically important Candida species
Classified according to their original intracellular function, the moonlighting proteins detected in the cell wall of C. albicans include:
Summary
A moonlighting protein is a single polypeptide chain that has a usually evolutionally conserved function but performs an additional unrelated function via a priori unexpected interactions with non-canonical molecular targets. Because of the tremendous number of combined functions (moonlighting vs “classic”) among moonlighting proteins, multiplied by the variable distribution of these functions between intracellular/extracellular compartments, a detailed classification of all moonlighting proteins will be problematic It has been recently proposed [9] to classify them into two large groups only, leaving aside many individual moonlighting proteins with unique features. Bacteria commonly non-conventionally secrete cytosolic proteins and expose them at their cell surface to interact with the host Many of these proteins have been confirmed to play important roles in biofilm formation, adhesion to the host cells and extracellular matrix, host tissue invasion, infection and virulence. We critically summarize the current state of knowledge on cell surface-exposed moonlighting proteins in the opportunistic pathogen Candida albicans, one of the most common fungal pathogens in humans and in several other closely related and medically important Candida species
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