Fungal secreted peptides and proteins: from cell homeostasis to pathogenesis

Proteomics and peptidomics are research fields with great potential to find new therapeutic targets, identify virulence factors, and reveal critical biological mechanisms in fungal diseases. For example, studying proteins allowed the identification of secreted aspartyl proteinases and peptides like candidalysin, which are significant players in candidiasis. The combination of proteomics tools with molecular methods can boost the research in the field and shed light on the understanding of intricated pathogenesis mechanisms. A substantial part of the pathogenesis can be explained by fungal-secreted factors such as proteins or peptides. For a long time, the interest in fungal secreted proteins has been mainly focused only on biotechnology applications, which produced important results (e.g., proteases applied to food industry, lignin decomposition, etc.). Knowledge on secreted fungal proteases from a biochemical perspective is still a matter of interesting discussion. The field presents an excellent opportunity to discover mechanisms related to immune evasion, tissue invasion, host signaling perturbation, and pathogenesis in general.

Considering the recent advances in proteomics using short gradients and searches with deep learning, for instance, the possibility of mapping peptides and proteins to significant biological processes has become more feasible than ever before. This technology allows us to investigate how the fungal proteases affect host cells' response on the tissue site of infection by interacting with protease-activated receptors or generating limited proteolysis, which can produce active peptides. Terminal amine isotopic labeling of substrates, for instance, is a technic valuable to accomplish this but remains unexplored in the field of medical mycology. This and other technologies highly used in other research fields can be valuable for fungal biology. The authors are highly encouraged to make a collaborative effort to promote advances in the field. Other technics that allow the investigation of fungal secreted proteins or peptides are also valuable, and descriptions of proteases with applications in biotechnology related to the pharmaceutical industry are welcome.

• Comprehensive reviews focusing on functions of secreted peptides and proteins;

• Original research highlighting pathogenesis mechanisms involving fungal secreted proteins or peptides;

• Original research proposing secreted proteins or peptides as clinical biomarkers;

• Original research highlighting secreted proteins or peptides as virulence factors;

• Methods, technology, or code presenting pipelines for investigating proteins and peptides of interest for the field of medical mycology;

• Brief research reports presenting advances in the biochemistry of fungal secreted peptides and proteins.

Keywords: virulence factors, tissue invasion, proteolysis, secreted proteins, secretome.

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