Breukink E, Wiedemann I, van Kraaij C, Kuipers O P, Sahl H G, de Kruijff B
Center of Biomembranes and Lipid Enzymology, Department of Biochemistry of Membranes, Institute for Biomembranes, Utrecht University, Padualaan 8, 3584 CH Utrecht, Netherlands.
Science. 1999 Dec 17;286(5448):2361-4. doi: 10.1126/science.286.5448.2361.
Resistance to antibiotics is increasing in some groups of clinically important pathogens. For instance, high vancomycin resistance has emerged in enterococci. Promising alternative antibiotics are the peptide antibiotics, abundant in host defense systems, which kill their targets by permeabilizing the plasma membrane. These peptides generally do not act via specific receptors and are active in the micromolar range. Here it is shown that vancomycin and the antibacterial peptide nisin Z use the same target: the membrane-anchored cell wall precursor Lipid II. Nisin combines high affinity for Lipid II with its pore-forming ability, thus causing the peptide to be highly active (in the nanomolar range).
在一些具有临床重要性的病原体群体中，对抗生素的耐药性正在增加。例如，肠球菌中已出现对万古霉素的高耐药性。有前景的替代抗生素是肽抗生素，其在宿主防御系统中大量存在，通过使质膜通透来杀死靶标。这些肽通常不通过特定受体起作用，且在微摩尔范围内具有活性。本文表明万古霉素和抗菌肽乳酸链球菌素Z使用相同的靶标：膜锚定的细胞壁前体脂质II。乳酸链球菌素对脂质II具有高亲和力并兼具成孔能力，因此使该肽具有高活性（在纳摩尔范围内）。
