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A Malassezia pseudoprotease dominates the secreted hydrolase landscape and is a potential allergen on skin

Lookup NU author(s): Professor John Common

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Abstract

© 2023 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). Malassezia globosa is abundant and prevalent on sebaceous areas of the human skin. Genome annotation reveals that M. globosa possesses a repertoire of secreted hydrolytic enzymes relevant for lipid and protein metabolism. However, the functional significance of these enzymes is uncertain and presence of these genes in the genome does not always translate to expression at the cutaneous surface. In this study we utilized targeted RNA sequencing from samples isolated directly from the skin to quantify gene expression of M. globosa secreted proteases, lipases, phospholipases and sphingomyelinases. Our findings indicate that the expression of these enzymes is dynamically regulated by the environment in which the fungus resides, as different growth phases of the planktonic culture of M. globosa show distinct expression levels. Furthermore, we observed significant differences in the expression of these enzymes in culture compared to healthy sebaceous skin sites. By examining the in situ gene expression of M. globosa's secreted hydrolases, we identified a predicted aspartyl protease, MGL_3331, which is highly expressed on both healthy and disease-affected dermatological sites. However, molecular modeling and biochemical studies revealed that this protein has a non-canonical active site motif and lacks measurable proteolytic activity. This pseudoprotease MGL_3331 elicits a heightened IgE-reactivity in blood plasma isolated from patients with atopic dermatitis compared to healthy individuals and invokes a pro-inflammatory response in peripheral blood mononuclear cells. Overall, our study highlights the importance of studying fungal proteins expressed in physiologically relevant environments and underscores the notion that secreted inactive enzymes may have important functions in influencing host immunity.

Publication metadata

Author(s): Chua W, Marsh CO, Poh SE, Koh WL, Lee MLY, Koh LF, Tang X-ZE, See P, Ser Z, Wang SM, Sobota RM, Dawson TL, Yew YW, Thng S, O'Donoghue AJ, Oon HH, Common JE, Li H

Publication type: Article

Publication status: Published

Journal: Biochimie

Year: 2024

Volume: 216

Pages: 181-193

Print publication date: 01/01/2024

Online publication date: 24/09/2023

Acceptance date: 22/09/2023

ISSN (print): 0300-9084

ISSN (electronic): 6183-1638

Publisher: Elsevier BV

URL: https://doi.org/10.1016/j.biochi.2023.09.023

DOI: 10.1016/j.biochi.2023.09.023

PubMed id: 37748748

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