More than Just Protein Degradation: The Regulatory Roles and Moonlighting Functions of Extracellular Proteases Produced by Fungi Pathogenic for Humans

Abstract

Extracellular proteases belong to the main virulence factors of pathogenic fungi. Their proteolytic activities plays a crucial role in the acquisition of nutrients from the external environment, destroying host barriers and defenses, and disrupting homeostasis in the human body, e.g., by affecting the functions of plasma proteolytic cascades, and playing sophisticated regulatory roles in various processes. Interestingly, some proteases belong to the group of moonlighting proteins, i.e., they have additional functions that contribute to successful host colonization and infection development, but they are not directly related to proteolysis. In this review, we describe examples of such multitasking of extracellular proteases that have been reported for medically important pathogenic fungi of the Candida, Aspergillus, Penicillium, Cryptococcus, Rhizopus, and Pneumocystis genera, as well as dermatophytes and selected endemic species. Additional functions of proteinases include supporting binding to host proteins, and adhesion to host cells. They also mediate self-aggregation and biofilm formation. In addition, fungal proteases affect the host immune cells and allergenicity, understood as the ability to stimulate a non-standard immune response. Finally, they play a role in the proper maintenance of cellular homeostasis. Knowledge about the multifunctionality of proteases, in addition to their canonical roles, greatly contributes to an understanding of the mechanisms of fungal pathogenicity.

Approaches to Control and Monitor Protease Levels in Chronic Wounds

“…Their footmark can be seen in various health issues, such as osteoarthritis via cartilage deterioration, [18] pulmonary disease by airway degeneration, [19] allergy, and cancer, among others. [20] In the wound environment, proteases could originate from microorganisms (bacteria and fungi) [21,22] or human body cells. The extracellular proteases of microorganisms degrade host barriers, in part by splitting cell junctions, and as a result, pave the way for the invasion of the pathogens.…”

“…The extracellular proteases of microorganisms degrade host barriers, in part by splitting cell junctions, and as a result, pave the way for the invasion of the pathogens. [21,22] Readers who are interested in the adverse effects of bacterial-origin proteases on wound healing can refer to a review article dedicated to this topic. [23] In the human and animal body, proteases are secreted by a variety of cells, including inflammatory cells, such as neutrophils, macrophages, and mast cells, as well as non-inflammatory cells, such as epithelial cells, endothelial cells, keratinocytes, and fibroblasts.…”

Moving beyond species: Fungal function in house dust provides novel targets for potential indicators of mold growth in homes

“…Genes associated with fungal growth also had associations with negative health effects in prior studies. The fungal alkaline protease gene alp1 (also known as the allergen Asp f 13 gene) was upregulated at 100% compared to 85% ERH and has strong correlations with asthma severity and respiratory dysfunction [39] and potential functions in promoting fungal growth and infection development in the host [115]. The hydrophobin gene associated with fungal spore surfaces, rodA (rodlet protein or rodlet layer), can evade human host immune responses [116,117].…”

Pityriasis Versicolor—A Narrative Review on the Diagnosis and Management

“…That process plays a pivotal role in facilitating a planktonic cellular state, which could contribute to colonisation. Furthermore, these proteases act as virulence factors, especially in skin with compromised barriers [29,30]. Poh et al demonstrated, through the use of a 3D acute wound model, that the Malassezia furfur secreted aspartyl protease 1 (MfSAP1) has the potential to disrupt wound re-epithelialisation [31].…”