Hubbard Alasdair Tm, Coates Anthony Rm, Harvey Richard D
Infection and Immunity Research Centre, Division of Clinical Sciences, St George's, University of London, London, UK.
Institute of Pharmaceutical Science, King's College London, London, UK.
J Antibiot (Tokyo). 2017 Oct;70(10):1020-1025. doi: 10.1038/ja.2017.90. Epub 2017 Aug 2.
HT61 and chlorhexidine (CHX) are both putative membrane-active antimicrobials, which non-specifically target the anionic lipids abundant in bacterial membranes. In model systems, the ability of these antimicrobials to partition into lipid monolayers and increase the permeability of lipid bilayers is dependent upon the presence and proportion of anionic lipids such as phosphatidylglycerol. Despite their apparent similarity in membrane affinity, we have found that HT61 and CHX differ in the extent to which they affect membrane integrity. HT61 was found to be capable of severely disrupting the lipid bilayer, resulting in lysis of Staphylococcus aureus membranes and the release of ATP from protoplasts. CHX, by contrast, does not disrupt the lipid bilayer to a sufficiently large degree to result in lysis of the membrane or release of ATP from S. aureus protoplasts. This suggests that although antimicrobials that interact with the membrane often have a common target, the action they have on the membrane may differ widely and may not be the primary mode of action of the antimicrobial.
HT61和洗必泰（CHX）都是公认的具有膜活性的抗菌剂，它们非特异性地靶向细菌膜中丰富的阴离子脂质。在模型系统中，这些抗菌剂分配到脂质单层并增加脂质双层通透性的能力取决于阴离子脂质（如磷脂酰甘油）的存在和比例。尽管它们在膜亲和力上有明显相似性，但我们发现HT61和CHX在影响膜完整性的程度上有所不同。研究发现HT61能够严重破坏脂质双层，导致金黄色葡萄球菌细胞膜裂解并使原生质体释放ATP。相比之下，CHX不会对脂质双层造成足够大程度的破坏，从而导致细胞膜裂解或金黄色葡萄球菌原生质体释放ATP。这表明，尽管与膜相互作用的抗菌剂通常有共同靶点，但它们对膜的作用可能差异很大，且可能不是抗菌剂的主要作用方式。
