Lipid Segregation Explains Selective Toxicity of a Series of Fragments Derived from the Human Cathelicidin LL-37
Lipid Segregation Explains Selective Toxicity of a Series of Fragments Derived from the Human Cathelicidin LL-37
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DOI：
10.1128/aac.00321-09
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发表时间：
2009-09-01
影响因子：
4.9
通讯作者：
Epand, Richard M.
中科院分区：
文献类型：
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作者：
Epand, Raquel F.;Wang, Guangshun;Epand, Richard M.
唯一的人类凯萨林菌素，37个残基的肽LL-37，表现出抗革兰氏阳性和革兰氏阴性细菌的抗微生物活性。我们研究了几个片段的LL-37，表现出不同的抗微生物活性，与膜的组合物模仿革兰氏阳性或革兰氏阴性细菌的细胞质膜相互作用的能力。这些片段如下：KR-12，LL-37的最小活性片段，具有序列KRIVQRIKDFLR，其仅对革兰氏阴性菌表现出抗微生物活性;较长的肽GF-17，其显示出抗革兰氏阳性以及革兰氏阴性细菌的抗微生物活性;和GF-17 D3，具有3个D-氨基酸残基，其也仅对革兰氏阴性细菌具有选择性。具有使阴离子脂质远离膜中的两性离子脂质聚集的能力的那些片段对在其细胞质膜中含有两性离子脂质以及阴离子脂质的细菌表现出选择性毒性，但对仅具有阴离子脂质的细菌不表现出选择性毒性。这一发现允许预测某些试剂的细菌物种选择性，并为设计专门针对革兰氏阴性菌的新抗菌剂铺平了道路。
The only human cathelicidin, the 37-residue peptide LL-37, exhibits antimicrobial activity against both gram-positive and gram-negative bacteria. We studied the ability of several fragments of LL-37, exhibiting different antimicrobial activities, to interact with membranes whose compositions mimic the cytoplasmic membranes of gram-positive or of gram-negative bacteria. These fragments are as follows: KR-12, the smallest active segment of LL-37, with the sequence KRIVQRIKDFLR, which exhibits antimicrobial activity only against gram-negative bacteria; a slightly smaller peptide, RI-10, missing the two cationic residues at the N and C termini of KR-12, which has been shown not to have any antimicrobial activity; a longer peptide, GF-17, which shows antimicrobial activity against gram-positive as well as gram-negative bacteria; and GF-17D3, with 3 D-amino-acid residues, which is also selective only for gram-negative bacteria. Those fragments with the capacity to cluster anionic lipids away from zwitterionic lipids in a membrane exhibit selective toxicity toward bacteria containing zwitterionic as well as anionic lipids in their cytoplasmic membranes but not toward bacteria with only anionic lipids. This finding allows for the prediction of the bacterial-species selectivity of certain agents and paves the way for designing new antimicrobials targeted specifically toward gram-negative bacteria.