Nisin Z, mutant nisin Z and lacticin 481 interactions with anionic lipids correlate with antimicrobial activity - A monolayer study

Nisin Z, mutant nisin Z and lacticin 481 interactions with anionic lipids correlate with antimicrobial activity - A monolayer study
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DOI:
10.1111/j.1432-1033.1996.00267.x
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发表时间:
1996-01-15
期刊:
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子:
--
通讯作者:
Kuipers, OP
Kuipers, OP
中科院分区:
其他
文献类型:
--
作者:
Demel, RA;Peelen, T;Kuipers, OP

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以气/水界面的单分子脂膜为模型膜,研究了抗生素乳链菌素的膜相互作用。天然抗菌素Nisin A和Nisin Z对阴离子脂类磷脂酰甘油和双(磷脂酰甘油)(心磷脂)有很高的亲和力。当表面压力大于32mN/m时,与两性离子磷脂或中性脂类的相互作用很小,乳链菌素、乳链菌素突变体和乳链菌素481的抗菌活性与阴离子脂类相互作用显著相关。结果表明,N-末端部分(残基1-22)主要穿透到脂相。20-21位柔性的降低对单层相互作用和活性有负面影响。Nisin的C-末端可能与阴离子脂类以单体或低聚形式相互作用。在阴离子和两性离子类脂的混合物中,相互作用在大约70mol/100mol的阴离子类脂中达到最大。革兰氏阳性细菌是乳链菌素的主要靶标,其特征是膜上含有高含量的阴离子脂类。对乳链菌肽敏感的细菌的脂类提取物形成的单层比对乳链菌素相对不敏感的细菌的单层渗透性更强。
Monomolecular layers of lipids at the air/water interface have been used as a model membrane to study membrane interactions of the lantibiotic nisin. The natural lantibiotics nisin A and nisin Z proved to have a high affinity for the anionic lipids phosphatidylglycerol and bis(phosphatidyl)glycerol (cardiolipin). The interaction with zwitterionic phopholipids or neutral lipids is very low at surface pressures higher than 32 mN/m. Nisin, nisin mutants and lacticin 481 show a remarkable correlation between antimicrobial activity and anionic lipid interaction. The results indicate that primarily the N-terminal part (residues 1-22) penetrates into the lipid phase. Reduction of the flexibility at positions 20-21 has a negative effect on monolayer interaction and activity. The C-terminal part is probably responsible for ionic interactions of nisin in monomeric or oligomeric form with anionic lipids. In mixtures of anionic and zwitterionic lipids maximal interactions are found at approximately 70 mol/100 mol anionic lipid. Gram-positive bacteria, which form the main target for nisin, are characterized by a high content of anionic lipids in the membrane. Monolayers formed of lipid extracts of bacteria sensitive to nisin were more strongly penetrated than those of bacteria relatively insensitive to nisin.