Johnston, M.D., Hanlon, Geoff, Denyer, Stephen and Lambert, R.J.W. (2003) Membrane damage to bacteria caused by single and combined biocides Journal of Applied Microbiology, 94 (6). pp. 1015-1023. ISSN 1364-5072 (In Press)Full text not available from this repository.
Aims: To examine the effect on the leakage of low molecular weight cytoplasmic constituents from Staphylococcus aureus using phenolics singly and in combination, and to see if the observations could be modelled using a non-linear dose response. Methods and Results: The rate of potassium, phosphate and adenosine triphosphate leakage was examined in the presence of chlorocresol and m-cresol. Individually, leakage was observed only at long contact times or high concentrations. Combined at these ineffective concentrations, the cytoplasmic pool of all constituents studied was released within minutes. Both chlorocresol and m-cresol were shown to have non-linear dose responses. A rate model for the combinations, which takes account of these non-linear responses, accurately predicted the observations. Conclusions: Antimicrobials, which when used alone exhibit a non-linear dose response, will also give a non-linear dose response in combination. The simple linear-additive model ignores the concept of the dilution coefficient and will always describe the phenomenon of synergy for combinations where one or more of the components has a dilution coefficient greater than one. This has been borne out by examination of the purported prime lesion of chlorocresol and m-cresol, alone and in combination. Significance and Impact of the Study: Studies aimed at producing synergistic mixtures of antimicrobials, which ignore the non-linear additive effect, may waste valuable research effort looking for a physiological explanation for an apparent synergy, where none, in-fact, exists. Patents granted on the basis of analyses using the linear-additive model for combinations of compounds with non-linear dose responses may no longer be supportable.
|Item Type:||Journal article|
|Uncontrolled Keywords:||inhibition, Staphylococcus aureus, synergy|
|Subjects:||C000 Biological and Biomedical Sciences > C500 Microbiology|
|DOI (a stable link to the resource):||10.1046/j.1365-2672.2003.01923.x|
|Faculties:||Faculty of Science and Engineering > School of Pharmacy and Biomolecular Sciences > Microbiology
Faculty of Science and Engineering > School of Pharmacy and Biomolecular Sciences
|Depositing User:||editor spbs|
|Date Deposited:||29 Nov 2006|
|Last Modified:||08 Dec 2016 11:28|
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