Anti‐biofilm activity of ultrashort cinnamic acid peptide derivatives against medical device‐related pathogens. (27th August 2015)

• Record Type: Journal Article
• Authors: Laverty, Garry; McCloskey, Alice P.; Gorman, Sean P.; Gilmore, Brendan F.
• Is Part Of: Journal of peptide science. Volume 21:Number 10(2015:Oct.)
• Page Start: 770
• Page End: 778
• Publication Date: 2015-08-27
• Subjects: Peptides -- Periodicals; Peptides -- Periodicals; 572.65
• DOI: 10.1002/psc.2805
• Languages: English
• ISSNs: 1075-2617

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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, <italic>Staphylococcus epidermidis</italic> and <italic>Staphylococcus aureus</italic>, 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‐NH<sub>2</sub> displays particular promise with minimum biofilm eradication concentration (MBEC) values of 125 µg/ml against methicillin sensitive (ATCC 29213) and resistant (ATCC 43300) <italic>S</italic>. <italic>aureus</italic> and activity shown against biofilm forms of <italic>Escherichia coli</italic> (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).</p> <p>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. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.</p> </abstract>