Skin Commensal Malassezia globosa Secreted Protease Attenuates Staphylococcus aureus Biofilm Formation

Abstract

Skin provides the first defense against pathogenic micro-organisms and is also colonized by a diverse microbiota. Phylogenetic analysis of whole skin microbiome at different skin sites in health and disease has generated important insights on possible microbial involvement in modulating skin health. However, functional roles of the skin microbial community remain unclear. The most common sebaceous skin commensal yeasts are the basidiomycetes, Malassezia. Here, we characterized the dominant secreted Malassezia globosa protease in culture and subsequently named it Malassezia globosa Secreted Aspartyl Protease 1 (MgSAP1). We defined recombinant MgSAP1's substrate cleavage profile using an unbiased, mass-spectrometry-based technique. We show that this enzyme is physiologically relevant as mgsap1 expression was detected on at least one facial skin site of 17 healthy human volunteers. In addition, we demonstrated that this protease rapidly hydrolyzes Staphylococcus aureus protein A, an important S. aureus virulence factor involved in immune evasion and biofilm formation. We further observed that MgSAP1 has anti-biofilm properties against S. aureus. Taken together, our study defines a role for the skin fungus Malassezia in inter-kingdom interactions and suggests that this fungus and the enzymes it produces may be beneficial for skin health.

Biology, diagnosis and treatment ofMalasseziadermatitis in dogs and cats Clinical Consensus Guidelines of the World Association for Veterinary Dermatology

“…is unusual in thickness (90–150 nm), morphology (inner spiralling/corrugation) and composition (predominance of (1 → 6)‐ß‐ D ‐glucan, trace of mannan with unusual polysaccharide assembly, chitin prominent in bud‐scar, lipid‐rich wall and capsule) (Figure ). Interaction with other commensal microbes might also influence pathogenicity and expression of virulence factors . Thus, these commensal yeasts are likely highly regulated by continuous interactions with the host immune system (Section 6) and these interactions ultimately determine whether the outcome is inflammation (i.e.…”

“…Laboratory data indicated that phospholipase production might act in synergism with biofilm formation (layers of adhering yeasts embedded in variable quantities of extracellular matrix) to induce or exacerbate skin lesions in dogs . By contrast, a secreted aspartyl protease from M. globosa inhibited S. aureus biofilm proliferation and rapidly hydrolysed protein A, a major staphylococcal virulence factor . A correlation between biofilm formation and other virulence factors (hydrophobicity, adherence) was observed amongst 60% of 16 clinical isolates of M. furfur .…”

The Skin Commensal Yeast Malassezia Triggers a Type 17 Response that Coordinates Anti-fungal Immunity and Exacerbates Skin Inflammation

“…It is generally believed that Malassezia actively promotes disease symptoms in predisposed atopic individuals, albeit firm evidence for this causal link is missing and the mechanistic basis has not been established. Alternatively, Malassezia may also exert a protective role in AD (Li et al, 2018).…”

The role of the skin microbiota in acne pathophysiology

“…This dual role of C. acnes is a feature that also extends to other skin microbes, for example Malassezia globosa . While generally accepted as the cause of seborrhoeic dermatitis, M. globosa has also been shown to secrete a potentially beneficial protease, which may prevent S. aureus biofilm formation (the role of fungal microbiota in acne is discussed later in this review) . Hence, many skin microbes may play dual roles in health and disease, and the differences in their function may lie at the strain or subspecies level …”

“…While generally accepted as the cause of seborrhoeic dermatitis, M. globosa has also been shown to secrete a potentially beneficial protease, which may prevent S. aureus biofilm formation (the role of fungal microbiota in acne is discussed later in this review). 42 Hence, many skin microbes may play dual roles in health and disease, and the differences in their function may lie at the strain or subspecies level. 16,[43][44][45][46] Multiple C. acnes studies have led to the classification of subspecies or types, each displaying a unique set of characteristics, activities and pathogenic potential.…”