Single-molecule interrogation of a bacterial sugar transporter allows the discovery of an extracellular inhibitor.
Single-molecule interrogation of a bacterial sugar transporter allows the discovery of an extracellular inhibitor.
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DOI：
10.1038/nchem.1695
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发表时间：
2013-08
期刊：
影响因子：
21.8
通讯作者：
Lingbing Kong;Leon Harrington;Qiuhong Li;S. Cheley;B. G. Davis;H. Bayley
中科院分区：
文献类型：
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作者：
Lingbing Kong;Leon Harrington;Qiuhong Li;S. Cheley;B. G. Davis;H. Bayley
荚膜多糖形成许多革兰氏阴性细菌周围的最外层保护层。目前还没有直接用于削弱这一层的抗生素。在致病性大肠杆菌E69中，蛋白质Wza在外膜上形成一个孔，将K30荚膜多糖从其合成位点转运到细胞外。因此，这是一个有前景的抗生素靶点。在这里，我们测试了各种各样的K30荚膜多糖在野生型Wza和突变体开放形式的孔通过电记录在平面脂质双层的hammet样模拟物。最有效的糖模拟物是非天然环状八糖八（6-脱氧-6-氨基）环麦芽糖八糖（am 8 γCD），它阻断了Wza的α-螺旋桶，这是一个可以从外部介质直接进入的位点。该糖模拟物抑制K30多糖在liveE中的转运。coliE69.随着保护性外膜的破坏，细菌可以被人体免疫系统识别和杀死。
Capsular polysaccharides form the outermost protective layer around many Gram-negative bacteria. Antibiotics aimed directly at weakening this layer are not yet available. In pathogenicEscherichia coliE69, a protein, Wza, forms a pore in the outer membrane that transports K30 capsular polysaccharide from its site of synthesis to the outside of the cell. This therefore represents a prospective antibiotic target. Here we test a variety of grommet-like mimics of K30 capsular polysaccharide on wild-type Wza and on mutant open forms of the pore by electrical recording in planar lipid bilayers. The most effective glycomimetic was the unnatural cyclic octasaccharide octakis(6-deoxy-6-amino)cyclomaltooctaose (am8γCD), which blocks the α-helix barrel of Wza, a site that is directly accessible from the external medium. This glycomimetic inhibited K30 polysaccharide transport in liveE. coliE69. With the protective outer membrane disrupted, the bacteria can be recognized and killed by the human immune system.