title: In vitro activity of human and animal cathelicidins against livestock-associated methicillin-resistant Staphylococcus aureus.
abstract: Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is an important zoonotic pathogen. An emerging problem in treating S. aureus infections is the increasing resistance against antibiotics. A possible way to overcome this issue is to boost the host immune system and one target are antimicrobial peptides (AMPs), especially cathelicidins. The aim of this study was to characterize the antimicrobial activity of cathelicidins from different animal species against LA-MRSA and to reveal whether major antimicrobial resistance mechanisms influence the bactericidal activity of these peptides. The MICs of 153 LA-MRSA field isolates for different cathelicidins (LL-37, mCRAMP, CAP18, BMAP-27 and BMAP-28) were analysed. The cathelicidin MICs of S. aureus RN4220 and isogenic transformants, that carried 14 functionally active antimicrobial resistance genes, were determined. These resistance genes have been identified in LA-MRSA and specify the resistance mechanisms active efflux, enzymatic inactivation and modification/protection/replacement of target sites. The data showed that mode MIC values for the cathelicidins did not differ among the LA-MRSA isolates of different animal origin. However, distinct differences were detected between the MIC values for the different cathelicidins. MIC values were lowest for bovine cathelicidins (BMAP-27 and BMAP-28) and highest for the human and mouse cathelicidins (LL-37 and mCRAMP). None of the tested antimicrobial resistance genes affected the antimicrobial activity of the cathelicidins. The findings obtained in this study support the hypothesis that cathelicidins might be a promising target to support the host defense against LA-MRSA, especially since the antimicrobial activity of these peptides is not affected by common staphylococcal antimicrobial resistance genes.
authors.affiliation: Department of Physiological Chemistry, University for Veterinary Medicine, Hannover, Germany; Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut, Neustadt-Mariensee, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Blodkamp
authors.affiliation: Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut, Neustadt-Mariensee, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Kadlec
authors.affiliation: Research group Biophysics, Research Centre Borstel, Borstel, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gutsmann
authors.affiliation: Department of Physiological Chemistry, University for Veterinary Medicine, Hannover, Germany.
authors.forename: Hassan Y
authors.initials: HY
authors.lastname: Naim
authors.affiliation: Department of Physiological Chemistry, University for Veterinary Medicine, Hannover, Germany; Research Center for Emerging Infections and Zoonoses (RIZ), University for Veterinary Medicine, Hannover, Germany. Electronic address: mkoeckbl@tiho-hannover.de.
authors.forename: Maren
authors.initials: M
authors.lastname: von Köckritz-Blickwede
authors.affiliation: Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut, Neustadt-Mariensee, Germany. Electronic address: stefan.schwarz@fli.bund.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwarz
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D054804:Cathelicidins / Q000302:isolation & purification / Q000494:pharmacology*; D002417:Cattle; D024881:Drug Resistance, Bacterial / Q000235:genetics; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents; D054804:Cathelicidins
keywords: Antimicrobial peptides; Antimicrobial resistance genes; MRSA; Minimal inhibitory concentration (MIC)