Membrane disruptive antimicrobial activities of human β-defensin-3 analogs.
Membrane disruptive antimicrobial activities of human β-defensin-3 analogs.
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人β-防御素-3类似物的膜破坏性抗菌活性。
DOI：
10.1016/j.ejmech.2014.08.021
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发表时间：
2015-02-16
影响因子：
6.7
通讯作者：
Ramamoorthy, Ayyalusamy
中科院分区：
文献类型：
--
作者：
Sudheendra, U. S.;Dhople, Vishnu;Datta, Aritreyee;Kar, Rajiv K.;Shelburne, Charles E.;Bhunia, Anirban;Ramamoorthy, Ayyalusamy
人β防御素-3 (HβD-3) 是一种宿主防御蛋白，对革兰氏阴性菌和革兰氏阳性菌均具有抗菌活性。由于该蛋白具有增强的耐盐性和针对革兰氏阳性金黄色葡萄球菌的活性，因此人们对该蛋白的功能非常感兴趣。在本研究中，研究了缺乏 N 和 C 末端区域的 HβD-3 类似物，以确定特定结构基序对革兰氏阳性菌和革兰氏阴性菌之间的抗菌活性和选择性的影响。圆二色性、荧光和固态核磁共振实验已用于研究 HβD3 类似物与各种模型膜的构象和作用模式，以模拟细菌内膜、外膜以及哺乳动物膜。我们的研究特别侧重于确定四个主要特征：（i）HβD3类似物与由两性离子PC或阴离子PE：PG囊泡和LPS组成的磷脂囊泡的相互作用； (ii) PC或PE:PG囊泡存在下HβD3-肽类似物的构象； (iii) HβD3类似物渗透由PC或PE:PG组成的磷脂囊泡的能力； (iv) 对细菌细胞和红细胞的活性。我们的结果推断，线性肽 L25P 及其环状形式 C25P 比 L21P 和 C21P 类似物更具活性。然而，它们的活性低于母肽，因此表明 N 末端结构域在其生物活性中的重要性。 L21P/C21P 和 L25P/C25P 活性的变化也表明 C 末端带正电荷的残基在提供选择性（特别是针对革兰氏阴性细菌）方面的重要性。
Human beta defensin-3 (HβD-3) is a host-defense protein exhibiting antibacterial activity towards both Gram-negative and Gram-positive bacteria. There is considerable interest in the function of this protein due to its increased salt tolerance and activity against Gram-positive S. aureus. In this study, analogs of HβD-3 devoid of N and C terminal regions are investigated to determine the influence of specific structural motif on antimicrobial activity and selectivity between Gram-positive and Gram-negative bacteria. Circular dichroism, fluorescence and solid-state NMR experiments have been used to investigate the conformation and mode of action of HβD3 analogs with various model membranes to mimic bacterial inner and outer membranes and also mammalian membranes. Our studies specifically focused on determining four major characteristics: (i) interaction of HβD3 analogs with phospholipid vesicles composed of zwitterionic PC or anionic PE:PG vesicles and LPS; (ii) conformation of HβD3-peptide analogs in the presence of PC or PE:PG vesicles; (iii) ability of HβD3 analogs to permeate phospholipid vesicles composed of PC or PE:PG; and (iv) activities on bacteria cells and erythrocytes. Our results infer that the linear peptide L25P and its cyclic form C25P are more active than L21P and C21P analogs. However, they are less active than the parent peptide, thus pointing towards the importance of the N terminal domain in its biological activity. The variation in the activities of L21P/C21P and L25P/C25P also suggest the importance of the positively charged residues at the C terminus in providing selectivity particularly to Gram-negative bacteria.
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影响因子：
--
作者：
Ghosh, Anirban;Datta, Aritreyee;Bhunia, Anirban
通讯作者：
Bhunia, Anirban
影响因子：
3.2
作者：
Ramamoorthy A
通讯作者：
Ramamoorthy A
影响因子：
4.8
作者：
Harder, J;Bartels, J;Schröder, JM
通讯作者：
Schröder, JM
影响因子：
15.9
作者：
GANZ, T;SELSTED, ME;LEHRER, RI
通讯作者：
LEHRER, RI
影响因子：
4.8
作者：
Schibli, DJ;Hunter, HN;Vogel, HJ
通讯作者：
Vogel, HJ