title: Cystatin C peptidomimetic derivative with antimicrobial properties as a potential compound against wound infections.
abstract: A peptidomimetic called A20 (Cystapep 1) structurally based upon the N-terminal fragment of human cystatin C is known to have strong antibacterial properties. A20 is characterized by high activity against several bacterial strains often isolated from infected wounds, including methicillin-resistant S. aureus (MRSA). In this work we wanted to explore the therapeutic potential of A20 in the treatment of wound infections. We examined, cytotoxicity, allergenicity and impact of A20 on the proliferation and viability of human keratinocytes. Furthermore, the previously described antimicrobial action of A20has been confirmed here with reference strains of bacteria and extended by several other species. The A20 was highly active against Gram-positive bacteria with minimal inhibitory (MIC) and minimal bactericidal concentrations (MBC) between 8 and 128μg/mL. A20 did not affect proliferation of primary human keratinocytes in concentrations up to 50μg/mL. At the same time, it did not activate Peripheral Blood Mononuclear Cells (PBMCs), including basophils or neutrophils in vitro. Interestingly A20 was found to display immunomodulatory functions as it influences the production of Th2 cytokines (IL-4 and IL-13) by activated PBMCs. It was also resistant to degradation for at least 48h in human plasma. The results indicate that A20 is effective against the multiantibiotic-resistant bacteria and has a high safety profile, which makes it a promising antimicrobial drug candidate.
authors.affiliation: Department of Clinical Immunology and Transplantology, Medical University of Gdańsk, Poland. Electronic address: pikula@gumed.edu.pl.
authors.forename: Michał
authors.initials: M
authors.lastname: Pikuła
authors.affiliation: Department of Biomedical Chemistry, Faculty of Chemistry, University of Gdańsk, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Smużyńska
authors.affiliation: Nencki Institute of Experimental Biology, Warsaw, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Krzystyniak
authors.affiliation: Department of Clinical Immunology and Transplantology, Medical University of Gdańsk, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Zieliński
authors.affiliation: Department of Clinical Immunology and Transplantology, Medical University of Gdańsk, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Langa
authors.affiliation: Department of Embryology, Medical University of Gdańsk, Poland.
authors.forename: Milena
authors.initials: M
authors.lastname: Deptuła
authors.affiliation: Department of Embryology, Medical University of Gdańsk, Poland.
authors.forename: Adriana
authors.initials: A
authors.lastname: Schumacher
authors.affiliation: Department of Allergology, Medical University of Gdańsk, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Łata
authors.affiliation: Department of Embryology, Medical University of Gdańsk, Poland.
authors.forename: Mirosława
authors.initials: M
authors.lastname: Cichorek
authors.affiliation: Department of Clinical Chemistry, Lund University, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Grubb
authors.affiliation: Department of Clinical Immunology and Transplantology, Medical University of Gdańsk, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Trzonkowski
authors.affiliation: Department of Biomedical Chemistry, Faculty of Chemistry, University of Gdańsk, Poland.
authors.forename: Franciszek
authors.initials: F
authors.lastname: Kasprzykowski
authors.affiliation: Department of Biomedical Chemistry, Faculty of Chemistry, University of Gdańsk, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Rodziewicz-Motowidło
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D055316:Cystatin C / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006801:Humans; D015603:Keratinocytes; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D057786:Peptidomimetics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014946:Wound Infection / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D055316:Cystatin C; D057786:Peptidomimetics
keywords: Cystatin C; Infections; Peptidomimetics; Wound healing