title: Anti-biofilm activity of ultrashort cinnamic acid peptide derivatives against medical device-related pathogens.
abstract: The threat of antimicrobial resistance has placed increasing emphasis on the development of innovative approaches to eradicate multidrug-resistant pathogens. Biofilm-forming microorganisms, for example, Staphylococcus epidermidis and Staphylococcus aureus, are responsible for increased incidence of biomaterial infection, extended hospital stays and patient morbidity and mortality. This paper highlights the potential of ultrashort tetra-peptide conjugated to hydrophobic cinnamic acid derivatives. These peptidomimetic molecules demonstrate selective and highly potent activity against resistant biofilm forms of Gram-positive medical device-related pathogens. 3-(4-Hydroxyphenyl)propionic)-Orn-Orn-Trp-Trp-NH2 displays particular promise with minimum biofilm eradication concentration (MBEC) values of 125 µg/ml against methicillin sensitive (ATCC 29213) and resistant (ATCC 43300) S. aureus and activity shown against biofilm forms of Escherichia coli (MBEC: 1000 µg/ml). Kill kinetics confirms complete eradication of established 24-h biofilms at MBEC with 6-h exposure. Reduced cell cytotoxicity, relative to Gram-positive pathogens, was proven via tissue culture (HaCaT) and haemolysis assays (equine erythrocytes). Existing in nature as part of the immune response, antimicrobial peptides display great promise for exploitation by the pharmaceutical industry in order to increase the library of available therapeutic molecules. Ultrashort variants are particularly promising for translation as clinical therapeutics as they are more cost-effective, easier to synthesise and can be tailored to specific functional requirements based on the primary sequence allowing factors such as spectrum of activity to be varied.
authors: Biomaterials, Biofilm and Infection Control Research Group, School of Pharmacy, Queen's University of Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK.
authors: Garry
authors: G
authors: Laverty
authors: Biomaterials, Biofilm and Infection Control Research Group, School of Pharmacy, Queen's University of Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK.
authors: Alice P
authors: AP
authors: McCloskey
authors: Biomaterials, Biofilm and Infection Control Research Group, School of Pharmacy, Queen's University of Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK.
authors: Sean P
authors: SP
authors: Gorman
authors: Biomaterials, Biofilm and Infection Control Research Group, School of Pharmacy, Queen's University of Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK.
authors: Brendan F
authors: BF
authors: Gilmore
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D001672:Biocompatible Materials; D018441:Biofilms / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002934:Cinnamates / Q000737:chemistry*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D002934:Cinnamates; D010455:Peptides; C029010:cinnamic acid
keywords: MBEC; antimicrobial; biofilm; biomaterials; kill kinetics; peptide