Abstract
Chronic inflammatory skin diseases like psoriasis alter the local skin microbiome and lead to complications such as persistent infection with opportunistic/pathogenic bacteria. Disease-associated changes in microbiota may be due to downregulation of epidermal antimicrobial proteins/peptides, such as antimicrobial protein chemerin. Here, we show that chemerin and its bioactive derivatives have differential effects on the viability of different genera of cutaneous bacteria. The lethal effects of chemerin are enhanced by bacterial-derived ROS-induced chemerin peptide oxidation and suppressed by stationary phase sigma factor RpoS. Insight into the mechanisms underlying changes in the composition of cutaneous bacteria during autoreactive skin disease may provide novel ways to mobilize chemerin and its peptide derivatives for maximum antimicrobial efficacy.
Highlights
To prevent pathologic outcomes, the skin must continuously confront a wide and diverse array of bacterial challenges
The skin defense system engages many components, including microbiota- and epidermis-derived antimicrobial factors (Kwiecien et al, 2019), suggesting that expression-level variations of these factors might play a pathogenic role in altering the cutaneous microbiome
In contrast to antimicrobial factors of microbial origin that can be expected to mainly affect the growth of other strains that compete for the same cutaneous niche, AMPs that are highly expressed in the epidermis such as chemerin may play a dominant role in restricting skin associated microbiota
Summary
The skin must continuously confront a wide and diverse array of bacterial challenges. Proteolytic cleavage at serine 157 in the carboxyl-terminus of Chem163S results in generation of Chem157S isoform that is effective in triggering chemotaxis of several types of immune cells (Yamaguchi et al, 2011). This isoform exhibits much stronger growth inhibitory potential compared with Chem163S against bacteria (Kulig et al, 2011; Godlewska et al, 2017). In contrast to C-terminal region responsible for chemotactic potential, antimicrobial activity is mainly associated with a domain localized in the middle of the chemerin sequence, Val66-Pro peptide (p4), which embodies the majority of chemerin’s
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