PXD033336

PXD033336 is an original dataset announced via ProteomeXchange.

Title	The human pathobiont Malassezia furfur secreted protease MfSAP1 regulates cell dispersal and exacerbates skin inflammation
Description	Malassezia forms the dominant eukaryotic microbial community on the human skin. The Malassezia genus possesses a repertoire of secretory hydrolytic enzymes involved in protein and lipid metabolism which alter the external cutaneous environment. The exact role of most Malassezia secreted enzymes, including those in interaction with the epithelial surface, are not well characterized. In this study, we compared the expression level of secreted proteases, lipases, phospholipases, and sphingomyelinases of Malassezia globosa in healthy subjects and seborrheic dermatitis or atopic dermatitis patients. We observed upregulated gene expression of the previously characterized secretory aspartyl protease MgSAP1 in both the lesional and non-lesional skin sites of affected compared to healthy subjects. To explore the functional roles of MgSAP1 in skin disease, we generated a knockout mutant of the homologous protease MfSAP1 in the genetically tractable Malassezia furfur. We observed the loss of MfSAP1 resulted in dramatic changes in the cell adhesion and dispersal in both culture and a human 3D reconstituted epidermis model. In a murine model of Malassezia colonization, we further demonstrated MfSAP1 contributes to inflammation as observed by reduced edema and myeloid pustule formation with the knockout mutant versus wildtype. Taken together, we show that this dominant secretory Malassezia aspartyl protease has an important role in enabling a planktonic cellular state that can potentially aid in colonization and additionally as a virulence factor in barrier-compromised skin, further highlighting the importance of considering the contextual relevance when evaluating the functions of secreted microbial enzymes.
HostingRepository	jPOST
AnnounceDate	2022-11-11
AnnouncementXML	Submission_2023-04-02_20:22:47.367.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Radoslaw Sobota
SpeciesList	scientific name: cellular organisms; NCBI TaxID: 131567;
ModificationList	S-carboxamidomethyl-L-cysteine; L-methionine sulfoxide; alpha-amino acetylated residue; deamidated L-glutamine; deamidated L-asparagine
Instrument	instrument

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-21 06:28:33	ID requested
1	2022-11-10 19:12:38	announced
⏵ 2	2023-04-02 20:22:48	announced	2023-04-03: Updated PubMed.

Goh JPZ, Ruchti F, Poh SE, Koh WLC, Tan KY, Lim YT, Thng STG, Sobota RM, Hoon SS, Liu C, O'Donoghue AJ, LeibundGut-Landmann S, Oon HH, Li H, Dawson TL, secreted protease Mfsap1 regulates cell dispersal and exacerbates skin inflammation. Proc Natl Acad Sci U S A, 119(49):e2212533119(2022) [pubmed]

submitter keyword: skin, fungi, protease, colonization, inflammation, extracellular matrix, label free quantification

Hao Li and Thomas L. Dawson
lab head
Radoslaw Sobota
contact affiliation	IMCB A-STAR Singapore
dataset submitter

jPOST dataset URI

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