【作者】 陈加喜； 陈翠霞； 徐海；

【Author】 Jiaxi Chen;Cuixia Chen;Hai Xu;Centre for Bioengineering and Biotechnology,China University of Petroleum (East China);

【机构】 生物工程与技术中心中国石油大学(华东)；

【摘要】 抗生素的滥用导致细菌的耐药性不断增加,而抗菌肽具有良好的抗菌活性,同时具有多样性和可修饰性,使人们对该新型抗菌药物的抗菌机理产生了浓厚兴趣。本组自主设计了两类阳离子短肽beta折叠肽（A9K）和螺旋肽G₃,发现二者都具有良好的抗菌活性,但由于多肽分子及其组装体尺寸均处于纳米水平,很难在分子层面观测到其具体的作用机理。因此,我们利用原子力显微镜在空气状态和生理环境下观察了抗菌肽的加入对于细菌的影响。研究发现,抗菌肽A9K自组装体可附着在细菌表面,随着时间的延长,造成细菌表面粗糙度增加,并伴随着细菌表面鼓泡行为的发生;相比而言,G₃分子在较低浓度下不发生自组装,以单分子状态存在于溶液中,随着与细菌作用时间的增长,细菌表面出现了褶皱、收缩,细菌高度轻微降低,说明G₃并没有使细菌外壁磷脂等大分子产生脱落,而是造成了细菌基质的泄漏。这些结果表明,这两种抗菌肽造成的不同抗菌机制主要与肽自身的结构相关,A9K的作用模式像是以"表面活性剂"模型对细菌外壁造成的破坏;而G₃则主要是以"打孔"的作用方式穿透细胞使基质外泄。更多还原

【Abstract】 With the increasing of the resistance bacteria due to the abuse of antibiotics, antimicrobial peptides with the diversity and modification had become one of the potential bactericidal agent. We have designed two kind of cationic short peptides simplized as ?-sheet peptide(A9 K) and ɑ-helix(G3). These two peptides were found to be efficient against E. coli with low toxicities to normal human cells. However, the detail mechanical of the two peptides were still unclear due to their nano-scale molecular size. Here we used atomic force microscopy(AFM) to observe the antibacterial mechanism of the two peptides in air and physiological environment. It was found that the self-assembles of A9 K can adhere to the surface of the bacteria. As a result, the surface roughness of bacteria increased with the incubation time and some bubbles were observed on the bacterial surface. We speculate that the insertion of A9 K causes the cell wall release, and gradually disintegrates the lipopolysaccharide and phospholipid bilayer, thereby achieving the antibacterial effect. On the other hand, G3 does not self-assemble and exists in solution as monomers. The bacterial surface showed wrinkles and shrinkage, and the bacteria height decreased slightly. These results indicate that the different antibacterial mechanisms caused by these two antimicrobial peptides, which are mainly related to the structure of the peptide itself, and the mode of action of A9 K is like the damage caused by the "surfactant-like" model on the outer wall of bacteria; G3 is more like penetrating the cells to make the matrix leak.更多还原