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

Autor: Chua W; Molecular Engineering Lab, Institute of Molecular and Cell Biology, Agency for Science Technology and Research, Singapore, 61 Biopolis Drive, Proteos, 138673, Singapore., Marsh CO; Department of Chemistry, National University of Singapore, 3 Science Drive 3, 117543, Singapore., Poh SE; Molecular Engineering Lab, Institute of Molecular and Cell Biology, Agency for Science Technology and Research, Singapore, 61 Biopolis Drive, Proteos, 138673, Singapore., Koh WL; Bioinformatics Institute, Agency for Science, Technology and Research, 30 Biopolis Street, #07-01, Matrix, 138671, Singapore., Lee MLY; Department of Chemistry, National University of Singapore, 3 Science Drive 3, 117543, Singapore., Koh LF; A∗STAR Skin Research Labs, Agency for Science, Technology and Research, 8A Biomedical Grove, #06-06, Immunos, 138648, Singapore., Tang XE; Molecular Engineering Lab, Institute of Molecular and Cell Biology, Agency for Science Technology and Research, Singapore, 61 Biopolis Drive, Proteos, 138673, Singapore., See P; Molecular Engineering Lab, Institute of Molecular and Cell Biology, Agency for Science Technology and Research, Singapore, 61 Biopolis Drive, Proteos, 138673, Singapore., Ser Z; Functional Proteomics Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, 61 Biopolis Drive, Proteos, 138673, Singapore., Wang SM; Functional Proteomics Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, 61 Biopolis Drive, Proteos, 138673, Singapore., Sobota RM; Functional Proteomics Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, 61 Biopolis Drive, Proteos, 138673, Singapore., Dawson TL Jr; A∗STAR Skin Research Labs, Agency for Science, Technology and Research, 8A Biomedical Grove, #06-06, Immunos, 138648, Singapore; College of Pharmacy, Department of Drug Discovery, Medical University of South Carolina, USA., Yew YW; National Skin Centre, National Healthcare Group, 1 Mandalay Rd, 308205, Singapore; Skin Research Institute of Singapore, Skin Research Institute of Singapore (SRIS), 17-01 LKC CSB, 11 Mandalay Rd, 308232, Singapore., Thng S; National Skin Centre, National Healthcare Group, 1 Mandalay Rd, 308205, Singapore; Skin Research Institute of Singapore, Skin Research Institute of Singapore (SRIS), 17-01 LKC CSB, 11 Mandalay Rd, 308232, Singapore., O'Donoghue AJ; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, United States., Oon HH; National Skin Centre, National Healthcare Group, 1 Mandalay Rd, 308205, Singapore; Skin Research Institute of Singapore, Skin Research Institute of Singapore (SRIS), 17-01 LKC CSB, 11 Mandalay Rd, 308232, Singapore., Common JE; A∗STAR Skin Research Labs, Agency for Science, Technology and Research, 8A Biomedical Grove, #06-06, Immunos, 138648, Singapore; Skin Research Institute of Singapore, Skin Research Institute of Singapore (SRIS), 17-01 LKC CSB, 11 Mandalay Rd, 308232, Singapore., Li H; Molecular Engineering Lab, Institute of Molecular and Cell Biology, Agency for Science Technology and Research, Singapore, 61 Biopolis Drive, Proteos, 138673, Singapore; Department of Chemistry, National University of Singapore, 3 Science Drive 3, 117543, Singapore. Electronic address: chmlihao@nus.edu.sg.
Jazyk: angličtina
Zdroj: Biochimie [Biochimie] 2024 Jan; Vol. 216, pp. 181-193. Date of Electronic Publication: 2023 Sep 24.
DOI: 10.1016/j.biochi.2023.09.023
Abstrakt: 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.
Competing Interests: Declaration of competing interest Conflict of Interest Statement for “A Malassezia pseudoprotease dominates the secreted hydrolase landscape and is a potential allergen on skin”. All authors declare no conflict of interest.
(Copyright © 2023 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)
Databáze: MEDLINE
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