Bacteria Modify Their Sensitivity to Chemerin-Derived Peptides by Hindering Peptide Association With the Cell Surface and Peptide Oxidation

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.

Redox Active Antimicrobial Peptides in Controlling Growth of Microorganisms at Body Barriers

“…The higher the activity of cytochrome bc 1 , the faster the rate of superoxide formation [ 88 ]. This is in line with increased ROS production and sensitivity to p4 in highly replicating bacteria requiring a high energy demand to sustain their growth [ 76 ]. However, it is also likely that other differences, such as an altered surface or cell membrane composition, may be responsible for the diverse effects of p4 on highly replicating bacteria compared to bacteria in stationary phase.…”

“…Considering all these factors necessary to build PMF, both membrane integrity and ETC proteins may provide novel targets for a new generation of antimicrobial compounds. These may include chemerin-derived p4, which is bactericidal against drug-resistant strains such as MRSA and can inhibit growth of either replicating microbes or to a lower extent bacteria in stationary phase [ 30 , 76 ].…”

Identification, Characterization, and Tissue Expression Pattern of Alternatively Spliced Transcript Variants of Mouse RARRES2 Gene

“…It was hypothesized that removal of inhibitory peptide enables structural accessibility of chemerin antimicrobial domain, and/or a release of internal antimicrobial peptide. 26 While four transcript variants of mouse RARRES2 encoding three protein isoforms are known, there is only one con rmed splice variant of human RARRES2 (NM_002889.4). This variant is translated into hChem163S precursor protein.…”

“…To do so, we employed E.coli and previously established protocols used to produce human recombinant chemerin. 26 We were able to produce and purify mChem163K and mChem162K and their derivatives, but we could not purify mChem153K. This include puri cation on NI-sepharose, ion exchange chromatography puri cation (MonoSP and MonoQ sepharose), Ni-sepharose based puri cation in denaturing or semi-denaturing conditions, construction of expression vector coding for mChem153K containing two His-tag sequences at the N and C terminus, various protein expression strains of E.coli (BL21, ArcticExpress, Rosetta).…”

Chemerin-Derived Peptide Val66-Pro85 Is Effective in Limiting Methicillin-Resistant S. aureus Skin Infection

“…Chemerin-derived Val 66 -Pro 85 peptide (p4, Table 1) embodies the majority of chemerin's antimicrobial activity (Banas et al, 2013). The 20-amino acid-long p4 chemerin peptide displays similar antimicrobial activities as active chemerin, although with increased efficacy and potency (Banas et al, 2013;Godlewska et al, 2017Godlewska et al, , 2019Godlewska et al, , 2020.…”