Adding selectivity to antimicrobial peptides:: Rational design of a multidomain peptide against Pseudomonas spp.
Adding selectivity to antimicrobial peptides:: Rational design of a multidomain peptide against Pseudomonas spp.
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DOI：
10.1128/aac.50.4.1480-1488.2006
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发表时间：
2006-04-01
影响因子：
4.9
通讯作者：
Shi, WY
中科院分区：
文献类型：
--
作者：
Eckert, R;Qi, FX;Shi, WY
目前可用的抗菌剂对细菌属和种具有广泛的杀灭作用。这些常规抗生素不分青红皂白地杀灭微生物会破坏本土微生物区系的生态平衡，往往会导致负面的临床后果。能够精确定位病原菌而不损害良性微生物的特定物种抗菌剂提供了避免这一问题的方法。在这次交流中，我们报告了第一个合成的靶向特异性抗菌肽G10KHc的成功创造，通过在一般杀伤肽(Novispirin GIO)中添加合理设计的假单胞菌特异性靶向部分(KH)。得到的嵌合肽对假单胞菌具有更强的杀菌活性和更快的杀灭动力学。而不是只有GIO一个人。这种增强的杀灭活性是由于假单胞菌外膜结合和穿透增加所致。细胞。这些特性在非靶标细菌的测试中没有观察到，这种特异性使G10KHc能够选择性地消除假单胞菌。来自不同的文化。这项工作为产生靶向特定的“智能”抗菌剂以补充目前可用的常规抗生素奠定了基础。
Currently available antimicrobials exhibit broad killing with regard to bacterial genera and species. Indiscriminate killing of microbes by these conventional antibiotics can disrupt the ecological balance of the indigenous microbial flora, often resulting in negative clinical consequences. Species-specific antimicrobials capable of precisely targeting pathogenic bacteria without damaging benign microorganisms provide a means of avoiding this problem. In this communication, we report the successful creation of the first synthetic, target-specific antimicrobial peptide, G10KHc, via addition of a rationally designed Pseudomonas-specific targeting moiety (KH) to a generally killing peptide (novispirin GIO). The resulting chimeric peptide showed enhanced bactericidal activity and faster killing kinetics against Pseudomonas spp. than GIO alone. The enhanced killing activities are due to increased binding and penetration of the outer membrane of Pseudomonas sp. cells. These properties were not observed in tests of untargeted bacterial species, and this specificity allowed G10KHc to selectively eliminate Pseudomonas spp. from mixed cultures. This work lays a foundation for generating target-specific "smart" antimicrobials to complement currently available conventional antibiotics.