Ioannou Christopher J, Hanlon Geoff W, Denyer Stephen P
Quest International, R and D, Kennington Road, Ashford, Kent TN24 0LT, United Kingdom.
Antimicrob Agents Chemother. 2007 Jan;51(1):296-306. doi: 10.1128/AAC.00375-06. Epub 2006 Oct 23.
Mode-of-action studies concluded that alkyldimethylbenzylammonium chloride (ADBAC) (a blend of C(12), C(14) and C(16) 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 10(5) to 1 x 10(9) CFU/ml at 35 degrees C. For ADBAC and DDAC, an increased rapidity of killing against S. aureus (final concentration, 2 x 10(9) CFU/ml) was observed at 35 degrees C compared to 25 degrees 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 mug/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.
作用机制研究得出结论,烷基二甲基苄基氯化铵(ADBAC)(C(12)、C(14)和C(16)烷基同系物的混合物)和双癸基二甲基氯化铵(DDAC)都是膜活性剂,它们具有细微不同的作用模式,反映了早期细胞与金黄色葡萄球菌的相互作用。在35℃下,接种量范围为1×10(5)至1×10(9) CFU/ml时,ADBAC和DDAC的最低抑菌浓度(MIC)行为相似,范围为0.4 ppm至1.8 ppm。与25℃相比,在35℃下观察到ADBAC和DDAC对金黄色葡萄球菌(终浓度为2×10(9) CFU/ml)的杀灭速度加快。两种药剂的杀灭浓度指数(η)均<2.5,温度影响η值。对泄漏和杀灭数据的检查表明,单一的泄漏标记并不表明细胞死亡。ADBAC和DDAC分别具有朗缪尔(L4)和高亲和力(H3/4)摄取等温线。在初次摄取结束时,ADBAC分子在细胞表面形成单层覆盖,而DDAC形成双层覆盖。在杀菌浓度下会迅速发生细胞泄漏,细胞内钾离子和260 nm吸收池按此严格顺序完全耗尽。在浓度为9μg/ml(分别为0.0278 mM和0.0276 mM)及以上时,观察到ADBAC和DDAC会导致自溶,同时细胞内钾离子池约有30%被耗尽。自溶导致了ADBAC和DDAC的致死性,尽管高浓度的杀菌剂可能抑制了自溶酶的活性。