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.
Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.
Publication Date: 2015-08-27 PubMed ID: 26310860DOI: 10.1002/psc.2805Google Scholar: Lookup
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- Journal Article
Summary
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This study explores the effectiveness of ultrashort tetra-peptide conjugated to hydrophobic cinnamic acid derivatives in eradicating biofilm-forming pathogens that pose a threat to medical devices.
Antimicrobial Resistance and Biofilms
- The paper first discusses the dangerous rise in antimicrobial resistant pathogens, which directly influences the increased pressures for new and innovative approaches to solve this problem.
- The pathogens in focus are two common biofilm-forming bacteria: Staphylococcus epidermidis and Staphylococcus aureus. These bacteria have been known to cause biomaterial infections leading to longer hospital stays and more serious patient health issues.
The Potential of Peptidomimetic Molecules
- The research delves into the potential solution of peptidomimetic molecules that have shown potent activity against resistant biofilm forms of Gram-positive medical device-related pathogens.
- Out of these molecules, the 3-(4-Hydroxyphenyl)propionic)-Orn-Orn-Trp-Trp-NH2 displays promising characteristics, shown by minimum biofilm eradication concentration (MBEC) values of 125 µg/ml against both methicillin sensitive and resistant S. aureus. It also showed activity against biofilm forms of Escherichia coli.
Effectiveness and Kill Kinetics
- According to the study, complete eradication of established 24-hour biofilms could happen within 6 hours of exposure at the MBEC value.
- Additionally, relative to Gram-positive pathogens, a drop in cytotoxicity to cells was recorded via tissue culture (using HaCaT) and haemolysis assays (using equine erythrocytes).
Prospects for Clinical Therapeutics
- The anti-biofilm activity of antimicrobial peptides, which naturally exist as part of the immune response, suggests promising prospects for their exploitation by the pharmaceutical industry.
- Especially, ultrashort variants of these molecules prove to be cost-effective, easier to synthesize, and tailor-specific to fit functional requirements based on the primary sequence. This feature allows for variations in factors like spectrum of activity.
Cite This Article
APA
Laverty G, McCloskey AP, Gorman SP, Gilmore BF.
(2015).
Anti-biofilm activity of ultrashort cinnamic acid peptide derivatives against medical device-related pathogens.
J Pept Sci, 21(10), 770-778.
https://doi.org/10.1002/psc.2805 Publication
Researcher Affiliations
- Biomaterials, Biofilm and Infection Control Research Group, School of Pharmacy, Queen's University of Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK.
- Biomaterials, Biofilm and Infection Control Research Group, School of Pharmacy, Queen's University of Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK.
- Biomaterials, Biofilm and Infection Control Research Group, School of Pharmacy, Queen's University of Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK.
- Biomaterials, Biofilm and Infection Control Research Group, School of Pharmacy, Queen's University of Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK.
MeSH Terms
- Anti-Bacterial Agents / adverse effects
- Anti-Bacterial Agents / chemistry
- Anti-Bacterial Agents / pharmacology
- Biocompatible Materials
- Biofilms / drug effects
- Cell Line
- Cell Survival / drug effects
- Cinnamates / chemistry
- Hemolysis / drug effects
- Humans
- Microbial Sensitivity Tests
- Peptides / adverse effects
- Peptides / chemistry
- Peptides / pharmacology
- Staphylococcus aureus / drug effects
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