Universität zu Köln

Elezagic, D., Morgelin, M., Hermes, G., Hamprecht, A., Sengle, G., Lau, D., Hoellriegl, S., Wagener, R., Paulsson, M., Streichert, T. and Klatt, A. R. (2019). Antimicrobial peptides derived from the cartilage.-specific C-type Lectin Domain Family 3 Member A (CLEC3A) - potential in the prevention and treatment of septic arthritis. Osteoarthritis Cartilage, 27 (10). S. 1564 - 1574. OXFORD: ELSEVIER SCI LTD. ISSN 1522-9653

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Abstract

Objective: To investigate the antimicrobial activity of peptides derived from C-type Lectin Domain Family 3 Member A (CLEC3A), shed light on the mechanism of antimicrobial activity and assess their potential application in prevention and treatment of septic arthritis. Design: We performed immunoblot to detect CLEC3A peptides in human cartilage extracts. To investigate their antimicrobial activity, we designed peptides and recombinantly expressed CLEC3A domains and used them to perform viable count assays using E.coli, P.aeruginosa and S.aureus. We investigated the mechanism of their antimicrobial activity by fluorescence and scanning electron microscopy, performed ELISA-style immunoassays and transmission electron microscopy to test for lipopolysaccharide binding and surface plasmon resonance to test for lipoteichoic acid (LTA) binding. We coated CLEC3A peptides on titanium, a commonly used prosthetic material, and performed fluorescence microscopy to quantify bacterial adhesion. Moreover, we assessed the peptides' cytotoxicity against primary human chondrocytes using MTT cell viability assays. Results: CLEC3A fragments were detected in human cartilage extracts. Moreover, bacterial supernatants lead to fragmentation of recombinant and cartilage-derived CLEC3A. CLEC3A-derived peptides killed E.coli, P.aeruginosa and S.aureus, permeabilized bacterial membranes and bound lipopolysaccharide and LTA. Coating CLEC3A antimicrobial peptides (AMPs) on titanium lead to significantly reduced bacterial adhesion to the material. In addition, microbicidal concentrations of CLEC3A peptides in vitro displayed no direct cytotoxicity against primary human chondrocytes. Conclusions: We identify cartilage-specific AMPs originating from CLEC3A, resolve the mechanism of their antimicrobial activity and point to a novel approach in the prevention and treatment of septic arthritis using potent, non-toxic, AMPs. (C) 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Elezagic, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Morgelin, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hermes, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hamprecht, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sengle, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lau, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoellriegl, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagener, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Paulsson, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Streichert, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Klatt, A. R. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-133343
DOI:	10.1016/j.joca.2019.06.007
Journal or Publication Title:	Osteoarthritis Cartilage
Volume:	27
Number:	10
Page Range:	S. 1564 - 1574
Date:	2019
Publisher:	ELSEVIER SCI LTD
Place of Publication:	OXFORD
ISSN:	1522-9653
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENGINEERED CHIMERIC PEPTIDES; CATHELICIDIN FAMILY; BINDING; EXPRESSION; SURFACE; LL-37; INTERLEUKIN-6; ANTIBIOTICS; RELEASE; AGENTS Multiple languages Orthopedics; Rheumatology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13334