Peptide dendrimers G3KL and TNS18 inhibit Pseudomonas aeruginosa biofilms
Peptide dendrimers G3KL and TNS18 inhibit Pseudomonas aeruginosa biofilms
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肽树枝状聚合物 G3KL 和 TNS18 抑制铜绿假单胞菌生物膜
DOI：
10.1007/s00253-019-09801-3
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发表时间：
2019-07-01
影响因子：
5
通讯作者：
Qiao, Mingqiang
中科院分区：
文献类型：
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作者：
Han, Xiao;Liu, Yujie;Qiao, Mingqiang
在此，我们报告了肽树枝状聚合物G3 KL和TNS 18，这是最近报道的控制多重耐药细菌，如金黄色葡萄球菌，铜绿假单胞菌，鲍曼不动杆菌，强烈抑制生物膜形成铜绿假单胞菌PA 14低于其最低抑菌浓度（MIC）值，在这种条件下，他们也强烈影响群集运动。然而，消除预形成的生物膜需要高于MIC值的浓度。扫描电镜观察和激光共聚焦扫描显微镜观察表明，肽树枝状聚合物能以剂量依赖的方式破坏生物膜的形态结构和厚度，甚至使生物膜完全分散。膜电位分析表明，用肽树枝状聚合物处理的细胞呈现荧光强度的增加，这表明细胞质膜可能是G3 KL和TNS 18的靶点，类似于多粘菌素B。RNA-seq分析表明，在arnBCADTEF操纵子调节脂质A修饰中导致对AMP的抗性的基因表达在这三种化合物之间受到不同的影响，表明每种化合物靶向细胞膜，但方式不同。对铜绿假单胞菌的增殖细胞和生物膜的有效活性表明肽树枝状聚合物G3 KL和TNS 18是用于治疗感染的临床开发的有希望的候选物。
Herein we report that peptide dendrimers G3KL and TNS18, which were recently reported to control multidrug-resistant bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii, strongly inhibit biofilm formation by P. aeruginosa PA14 below their minimum inhibitory concentration (MIC) value, under which conditions they also strongly affect swarming motility. Eradication of preformed biofilms, however, required concentrations above the MIC values. Scanning electron microscopy observation and confocal laser scanning micrographs showed that peptide dendrimers can destroy the biofilm morphological structure and thickness in a dose-dependent manner, even make the biofilm dispersed completely. Membrane potential analysis indicated that planktonic cells treated with peptide dendrimers presented an increase in fluorescence intensity, suggesting that cytoplasmic membrane could be the target of G3KL and TNS18 similarly to polymyxin B. RNA-seq analysis showed that the expressions of genes in the arnBCADTEF operon-regulating lipid A modification resulting in resistance to AMPs are differentially affected between these three compounds, suggesting that each compound targets the cell membrane but in different manner. Potent activity on planktonic cells and biofilms of P. aeruginosa suggests that peptide dendrimers G3KL and TNS18 are promising candidates of clinical development for treating infections.