Broxton P, Woodcock P M, Heatley F, Gilbert P
J Appl Bacteriol. 1984 Aug;57(1):115-24. doi: 10.1111/j.1365-2672.1984.tb02363.x.
The interaction between some polyhexamethylene biguanides and the cell envelope of Escherichia coli has been investigated. An amine-ended dimer, (AED, n = 2), a polydisperse mixture (ICI plc) available as the active ingredient of Vantocil IB, (PHMB, n = 5.5), and a high molecular weight fraction, (HMW, n = greater than or equal to 10) of PHMB were used. The sensitivity of batch cultures depleted of magnesium (M-dep), phosphorus (P-dep) or glycerol (C-dep) towards the biocides was assessed by monitoring the rate and extent of potassium ion leakage. P-dep suspensions were particularly resistant to all these agents and possessed less than half the quantity of phospholipid of other cell types. This was compensated for by a proportionate increase in fatty acid and neutral lipid content of the cells. The reduction in phospholipid content was accounted for by decreases in phosphatidylglycerol (PG) and phosphatidylethanolamine (PE). Diphosphatidylglycerol (DPG) and phosphatidylserine (PS) content of the cultures remained unaffected by the depleting nutrient. Fourier-transform n.m.r. spectroscopy was used to study proton nuclei during the interaction of HMW, AED and PHMB with various phospholipid-vesicle preparations. The results strongly suggest that the biocides acted preferentially on the acidic phospholipids PG and DPG, rather than towards PE or PS. Resistance of P-dep cultures therefore reflected reductions in PG content. A molecular basis for the interaction of these compounds and membranes is proposed.
已对某些聚六亚甲基双胍与大肠杆菌细胞包膜之间的相互作用进行了研究。使用了一种胺端二聚体(AED,n = 2)、一种作为Vantocil IB活性成分的多分散混合物(ICI plc)(PHMB,n = 5.5)以及PHMB的高分子量级分(HMW,n≥10)。通过监测钾离子泄漏的速率和程度,评估了缺乏镁(M-dep)、磷(P-dep)或甘油(C-dep)的分批培养物对这些杀菌剂的敏感性。P-dep悬浮液对所有这些药剂特别耐药,其磷脂含量不到其他细胞类型的一半。细胞中脂肪酸和中性脂质含量的相应增加对此起到了补偿作用。磷脂含量的减少是由磷脂酰甘油(PG)和磷脂酰乙醇胺(PE)的减少所致。培养物中二磷脂酰甘油(DPG)和磷脂酰丝氨酸(PS)的含量不受营养物质耗尽的影响。利用傅里叶变换核磁共振光谱研究了HMW、AED和PHMB与各种磷脂囊泡制剂相互作用过程中的质子核。结果强烈表明,这些杀菌剂优先作用于酸性磷脂PG和DPG,而不是PE或PS。因此,P-dep培养物的耐药性反映了PG含量的降低。提出了这些化合物与膜相互作用的分子基础。