Rana F R, Macias E A, Sultany C M, Modzrakowski M C, Blazyk J
Department of Chemistry, College of Osteopathic Medicine, and Ohio University, Athens 45701.
Biochemistry. 1991 Jun 18;30(24):5858-66. doi: 10.1021/bi00238a008.
The role of the outer membrane and lipopolysaccharide (LPS) in the interaction between the small cationic antimicrobial peptide magainin 2 and the Gram-negative cell envelope was studied by FT-IR spectroscopy. Magainin 2 alters the thermotropic properties of the outer membrane-peptidoglycan complexes from wild-type Salmonella typhimurium and a series of LPS mutants which display differential susceptibility to the bactericidal activity of cationic antibiotics. These results are correlated with the LPS phosphorylation pattern and charge (characterized by high-resolution 31P NMR) and outer membrane lipid composition, and are compared to the bactericidal susceptibility. LPS mutants show a progressive loss of resistance to killing by magainin 2 as the length of the LPS polysaccharide moiety decreases. Disordering of the outer membrane lipid fatty acyl chains by magainin 2, however, depends primarily upon the magnitude of LPS charge rather than the length of the LPS polysaccharide, contradicting the proposal by Weiss et al. [Weiss, J., Beckerdite-Quagiata, S., & Elsbach, P. (1980) J. Clin. Invest. 65, 619-628] that the sugar side chain of LPS shields the negative charges of the outer membrane surface. While disruption of outer membrane structure most likely is not the primary factor leading to cell death, the susceptibility of Gram-negative cells to magainin 2 is associated with factors that facilitate the transport of the peptide across the outer membrane, such as the magnitude and location of LPS charge, the concentration of LPS in the outer membrane, outer membrane molecular architecture, and the presence or absence of the O-antigen side chain.
通过傅里叶变换红外光谱（FT-IR）研究了外膜和脂多糖（LPS）在小阳离子抗菌肽蛙皮素2与革兰氏阴性菌细胞壁相互作用中的作用。蛙皮素2改变了野生型鼠伤寒沙门氏菌以及一系列对阳离子抗生素杀菌活性表现出不同敏感性的LPS突变体的外膜-肽聚糖复合物的热致性质。这些结果与LPS磷酸化模式和电荷（通过高分辨率31P NMR表征）以及外膜脂质组成相关，并与杀菌敏感性进行了比较。随着LPS多糖部分长度的减少，LPS突变体对蛙皮素2杀伤的抗性逐渐丧失。然而，蛙皮素2对外膜脂质脂肪酰链的无序化作用主要取决于LPS电荷的大小，而非LPS多糖的长度，这与Weiss等人[Weiss, J., Beckerdite-Quagiata, S., & Elsbach, P. (1980) J. Clin. Invest. 65, 619-628]提出的LPS糖侧链屏蔽外膜表面负电荷的观点相矛盾。虽然外膜结构的破坏很可能不是导致细胞死亡的主要因素，但革兰氏阴性菌对蛙皮素2的敏感性与促进肽跨外膜转运的因素有关，如LPS电荷的大小和位置、外膜中LPS的浓度、外膜分子结构以及O抗原侧链的存在与否。
