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Antimicrobial Agents and Chemotherapy, January 2007, p. 296-306, Vol. 51, No. 1
0066-4804/07/$08.00+0     doi:10.1128/AAC.00375-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Action of Disinfectant Quaternary Ammonium Compounds against Staphylococcus aureus{triangledown}

Christopher J. Ioannou,1* Geoff W. Hanlon,2 and Stephen P. Denyer3

Quest International, Ashford, Kent TN24 0LT, United Kingdom,1 School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton BN2 4GJ, United Kingdom,2 Welsh School of Pharmacy, Cardiff University, Cardiff CF1 3XF, United Kingdom3

Received 27 March 2006/ Returned for modification 21 July 2006/ Accepted 17 October 2006

Mode-of-action studies concluded that alkyldimethylbenzylammonium chloride (ADBAC) (a blend of C12, C14 and C16 alkyl homologues) and didecyldimethylammonium chloride (DDAC) are both membrane-active agents, possessing subtly different modes of action reflecting early cell interactions against Staphylococcus aureus. ADBAC and DDAC exhibited similar MIC behaviors from 0.4 ppm to 1.8 ppm over an inoculum range of 1 x 105 to 1 x 109 CFU/ml at 35°C. For ADBAC and DDAC, an increased rapidity of killing against S. aureus (final concentration, 2 x 109 CFU/ml) was observed at 35°C compared to 25°C. Concentration exponents ({eta}) for killing were <2.5 for both agents, and temperature influenced the {eta} value. Examination of leakage and kill data suggested that a single leakage marker was not indicative of cell death. ADBAC and DDAC possessed Langmuir (L4) and high-affinity (H3/4) uptake isotherms, respectively. ADBAC molecules formed a single monolayer of coverage of cells at the end of primary uptake, and DDAC formed a double monolayer. Rapid cell leakage occurred at bactericidal concentrations, with total depletion of the intracellular potassium and 260-nm-absorbing pools released in this strict order. Autolysis was observed for ADBAC and DDAC at concentrations of 9 µg/ml (0.0278 mM and 0.0276 mM, respectively) and above, together with the depletion of approximately 30% of the internal potassium pool. Autolysis contributed to ADBAC and DDAC lethality, although high biocide concentrations may have inhibited autolytic enzyme activity.

* Corresponding author. Mailing address: Quest International, R&D, Kennington Road, Ashford, Kent TN24 0LT, United Kingdom. Phone: 44 (0) 1233 644405. Fax: 44 (0) 1233 644096. E-mail: chris.ioannou{at}questintl.com.

{triangledown} Published ahead of print on 23 October 2006.

Antimicrobial Agents and Chemotherapy, January 2007, p. 296-306, Vol. 51, No. 1
0066-4804/07/$08.00+0     doi:10.1128/AAC.00375-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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