Activity and selectivity of histidine-containing lytic peptides to antibiotic-resistant bacteria
Activity and selectivity of histidine-containing lytic peptides to antibiotic-resistant bacteria
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DOI：
10.1007/s00203-012-0810-5
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发表时间：
2012-09-01
影响因子：
2.8
通讯作者：
Liang, Jun F.
中科院分区：
文献类型：
--
作者：
Kharidia, Riddhi;Tu, Zhigang;Liang, Jun F.
裂解肽是一类对抗生素耐药细菌有活性，但对组织细胞有较高毒性的膜作用肽。在这里，我们报道了通过用组氨酸取代裂解肽模板中相应的赖氨酸/精氨酸残基来构建新的裂解肽衍生物。得到的裂解肽对包括耐甲氧西林金黄色葡萄球菌在内的耐抗生素细菌具有相同的杀伤力，但对细菌的选择性大大提高。当与共培养的细菌和组织细胞孵育时，这些含有组氨酸的裂解肽衍生物选择性地杀死细菌，但不会对共培养的人类细胞产生影响。膜插入和肽猝灭研究表明，组氨酸质子化控制的肽与细胞膜的相互作用决定了裂解肽衍生物的细菌选择性。与母体多肽相比，裂解多肽衍生物与细菌结合能力强，并能深入细菌细胞膜。因此，含有组氨酸的裂解肽代表了一类新的针对细菌感染的抗菌肽，在这种抗菌肽中已经产生了抗生素耐药性。
Lytic peptides are a group of membrane-acting peptides that are active to antibiotic-resistant bacteria but demonstrate high toxicity to tissue cells. Here, we reported the construction of new lytic peptide derivatives through the replacement of corresponding lysine/arginine residues in lytic peptide templates with histidines. Resulting lytic peptides had the same lethality to antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus, but showed greatly improved selectivity to bacteria. When incubated with co-cultured bacteria and tissue cells, these histidine-containing lytic peptide derivatives killed bacteria selectively but spared co-cultured human cells. Membrane insertion and peptide-quenching studies revealed that histidine protonation controlled peptide interactions with cell membranes determined the bacterial selectivity of lytic peptide derivatives. Compared with parent peptides, lytic peptide derivatives bound to bacteria strongly and inserted deeply into the bacterial cell membrane. Therefore, histidine-containing lytic peptides represent a new group of antimicrobial peptides for bacterial infections in which the antibiotic resistance has developed.