Document Type

Theses, Ph.D


Available under a Creative Commons Attribution Non-Commercial Share Alike 4.0 International Licence



Publication Details

Successfully submitted for the award of Doctor of Philosophy to the Technological University Dublin, November, 2009


The food industry has shown increased interest for novel natural antimicrobials due to consumer demand for foods with fewer synthetic additives, increased safety, quality and shelf-life. Concurrently, the emergence of drug resistant bacteria substantiates the need for newer antimicrobial agents. Alternative strategies include the use of novel antimicrobials, such as fatty acid derivatives, essential oils and bacteriocins, with proven antimicrobial properties against a diverse range of bacteria. This study investigated novel carbohydrate fatty acid (CF A) derivatives for their antibacterial activity against a range of pathogenic and spoilage bacteria. A series of mono-substituted CF A derivatives using lauric and caprylic acids were synthesized. Chemical routes allowing the attachment of the fatty acid as either an ester or ether to the monosaccharide 6-hydroxyl were developed. Structure/activity relationship studies of antimicrobial efficacy allowed some insight into the mechanism of action of these compounds. In addition, selected essential oil (EO) individual components and nisin, both alone and in combination, were also assessed for possible combination strategies with CF A derivatives. Minimum inhibitory concentration (MIC), ICso values, increase in lag phase and decrease in maximum specific growth rate were determined. Leakage of intracellular material absorbing at 260nm, Live/Dead BacLight fluorescence and ATP BacTiterGlo luminescence assays assessed membrane disrupting effects. Furthermore, a Phenotypic MicroArray assay was used to investigate bacterial cell response in the absence and presence of CF A derivatives. The laurate ether of methyl a-D-glucopyranoside (9a) and laurate ester of methyl a-D-mannopyranoside (4c) showed the highest growth-inhibitory effect. CFA derivatives were significantly more effective against Gram positive than Gram negative bacteria. The analysis of both ester and ether fatty acid derivatives of the same carbohydrate, in tandem with alpha and beta configuration of the carbohydrate moiety suggest that the carbohydrate moiety is involved in the antimicrobial activity of the fatty acid derivatives and that the nature of the bond also has a significant effect on efficacy. Membrane damage was observed and may account for at least a component of the mode of action of these compounds. The ATP assay and phenotypic responses suggested that another mechanism of action might also account for the antimicrobial activity of the beta lauric ether derivative (compound 9b). Carvacrol and thymol were found to have the highest antimicrobial activity, followed by citral. Nisin in combination with carvacrol, thymol and citral showed additive effects against Listeria spp. The antimicrobial effect of the combination was improved by lowering the pH from neutral to pH6. CF A derivatives with different structures have great potential for developing antibacterial agents relevant to the food and health care industries. Nisin in combination with individual EO components could lead to useful efficacy as an alternative natural preservative.


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