Moonlighting proteins in medically relevant fungi

Moonlighting proteins represent an intriguing area of cell biology, due to their ability to perform two or more unrelated functions in one or many cellular compartments. These proteins have been described in all kingdoms of life and are usually constitutively expressed and conserved proteins with housekeeping functions. Although widely studied in pathogenic bacteria, the information about these proteins in pathogenic fungi is scarce, but there are some reports of their functions in the etiological agents of the main human mycoses, such as Candida spp., Paracoccidioides brasiliensis, Histoplasma capsulatum, Aspergillus fumigatus, Cryptococcus neoformans, and Sporothrix schenckii. In these fungi, most of the described moonlighting proteins are metabolic enzymes, such as enolase and glyceraldehyde-3-phosphate dehydrogenase; chaperones, transcription factors, and redox response proteins, such as peroxiredoxin and catalase, which moonlight at the cell surface and perform virulence-related processes, contributing to immune evasion, adhesions, invasion, and dissemination to host cells and tissues. All moonlighting proteins and their functions described in this review highlight the limited information about this biological aspect in pathogenic fungi, representing this a relevant opportunity area that will contribute to expanding our current knowledge of these organisms’ pathogenesis.