pH-Dependent Expression, Stability, and Activity ofMalassezia restrictaMrLip5 Lipase

Abstract

Background The lipophilic yeasts Malassezia spp. are normally resident on the surface of the human body, and often associated with various skin diseases. Of the 18 known Malassezia spp., Malassezia restricta is the most predominantly identified Malassezia sp. found on the human skin. Malassezia possesses a large number of genes encoding lipases to degrade human sebum triglycerides into fatty acids, which are required not only for their growth, but also trigger skin diseases. Previously, we have shown that MrLIP5 (MRET_0930), one of the 12 lipase genes in the genome of M. restricta , and is the most frequently expressed lipase gene in the scalp of patients with dandruff. Objective In this study, we aimed to analyze the activity, stability, and expression of MrLip5, with particular focus on pH. Methods We heterologously expressed MrLip5 in Escherichia coli , and purified and analyzed its activity and expression under different pH conditions. Results We found that MrLip5 was most active and stable and highly expressed under alkaline conditions, which is similar to that of the diseased skin surface. Conclusion Our results suggest that the activity and expression of MrLip5 are pH-dependent, and that this lipase may play an essential role at the M. restricta -host interface during disease progression.

Epidermal barrier impairment predisposes for excessive growth of the allergy‐associated yeast Malassezia on murine skin

“…In addition, the hydrolysis of lipids by lipases may affect the acidic pH of the skin, as it is the case for bacterial lipases, 87,88 while enzyme activity itself is affected by pH. 89,90 While homeostatic immunity is central for controlling and restraining commensal organisms, 3 Irrespective of such putative additional factors, our results provide important novel insights into how the Malassezia-host interplay is impacted in AD-like skin and how it may add to the inflammatory pathology. Furthermore, it identifies an important role of MC903 in the modulation of skin fungal homeostasis, which should be considered for pharmacological use of calcipotriol and other Vitamin D analogs against skin carcinomas 91,92 and psoriasis (Dovonex®).…”

“…Phospholipases are considered virulence factors in many pathogenic fungi due to their potential to damage host cell membranes, 86 which can further aggravate barrier disruption and cause inflammation by inducing host cell lysis and subsequent release of danger‐associated molecular patterns. In addition, the hydrolysis of lipids by lipases may affect the acidic pH of the skin, as it is the case for bacterial lipases, 87,88 while enzyme activity itself is affected by pH 89,90 …”

Heat-killed Lacticaseibacillus paracasei GMNL-653 ameliorates human scalp health by regulating scalp microbiome

“…M. restricta lipases of MrLip1 or MrLip2 could hydrolyze mono- and diacylglycerol, and MrLip3 could hydrolyze mono-, di, and tri-acylglycerol [ 39 ]. MrLip5 lipase plays an essential role in M. restricta -host interfere during disease progression, and the MrLip5 lipase encoded by the genome of M. restricta shows stable activity and high expression under alkaline condition [ 40 ]. In our study, the abundance of M. restricta was not statistically different among the scalp samples collected before and after the use of heat-killed GMNL-653 shampoo in all subjects (Fig.…”

Epidermal barrier dysregulation in atopic skin predisposes for excessive growth of the allergy-associated yeastMalassezia

“…In addition, the hydrolysis of lipids by lipases may affect the acidic pH of the skin, as it is the case for bacterial lipases, 87,88 while enzyme activity itself is affected by pH. 89,90 Therefore, enhanced phospholipase expression by Malassezia may allow the fungus to better thrive on the host skin but may also contribute to disease pathogenesis. Another known fungal determinant associated with skin inflammation is secreted aspartyl protease 1 (SAP1), which was found to be highly expressed in AD lesional skin.…”