Targeted sequencing of skin commensalsecreted hydrolases reveals systemicchange ofcutaneous statein skin diseases

The skin is colonized by a rich microbial community. Malassezia globosa, adominant skin fungal species, possesses a repertoire of secreted hydrolytic enzyme genes whose functions are poorly understood. In this study, we designed a targeted RNAsequencing assay to quantify gene expression of M. globosasecreted proteases, lipases, phospholipases and sphingomyelinases. We observed that enzyme gene expression is dynamically regulated by their environment,as evident from the significant difference between in vitro culture versus healthy skin. To study the relevance of these enzymes in disease, we analyzed the M. globosa secreted enzyme expressionin patients with atopic dermatitis or seborrheic dermatitis. We observed a clear shift in enzyme expression in both the diseased and uninvolved skin sites of these patients compared to the healthy subjects. Our study shows that M. globosa responds to a global change in skin environment in individuals pre-disposed to disease, and the secreted hydrolases can serve as a marker of this altered cutaneous state