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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Adaptive mutations in the signal peptide of the type 1 fimbrial adhesin of uropathogenic Escherichia coli
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Adaptive mutations in the signal peptide of the type 1 fimbrial adhesin of uropathogenic Escherichia coli

机译：尿路致病性大肠杆菌1型纤维粘附素信号肽的适应性突变

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摘要

Signal peptides (SPs) are critical for protein transport across cellular membranes, have a highly conserved structure, and are cleaved from the mature protein upon translocation. Here, we report that naturally occurring mutations in the SP of the adhesive, tip-associated subunit of type 1 fimbriae (FimH) are positively selected in uropathogenic Escherichia coli. On the one hand, these mutations have a detrimental effect, with reduced FimH transport across the inner membrane, fewer FimH and fimbriae expressed on the bacterial surface, and decreased bacterial adhesion under flow conditions. On the other hand, the fimbriae expressed by the mutants are significantly longer on average, with many fimbriae able to stretch to > 20 μm in length. More surprisingly, the SP mutant bacteria display an increased ability to resist detachment from the surface upon a switch from high to low flow. This functional effect of longer fimbriae highlights the importance of the nonadhesive fimbrial rod for adhesive function. Also, whereas bacterial adhesion to bladder epithelial cells was preserved in most mutants, binding to and killing by human neutrophils was decreased, providing an additional reason the SP mutations are relatively common among uropathogenic strains. Thus, this study demonstrates how mutations in an SP, while decreasing transport function and not affecting the final structure of the translocated protein, can lead to functional gains of the extracellular organelles that incorporate the protein and overall adaptive changes in the organism's fitness.
机译：信号肽（SP）对于跨细胞膜的蛋白质运输至关重要，具有高度保守的结构，并且在易位时会从成熟蛋白质上裂解下来。在这里，我们报告在尿路致病性大肠杆菌中积极选择了黏附剂，与尖端相关的1型菌毛（FimH）亚基SP的自然发生突变。一方面，这些突变具有有害作用，减少了FimH跨内膜的运输，减少了细菌表面表达的FimH和菌毛，并降低了流动条件下的细菌粘附。另一方面，突变体表达的菌毛平均长得多，其中许多菌毛的长度可以拉伸到> 20μm。更令人惊讶的是，当从高流量转换为低流量时，SP突变细菌显示出更高的抵抗从表面脱离的能力。较长菌丝的这种功能效果突出了非粘性纤维棒对粘附功能的重要性。而且，尽管在大多数突变体中细菌粘附于膀胱上皮细胞的情况得以保留，但与人嗜中性粒细胞的结合和杀伤力却降低了，这提供了另一个原因，即在泌尿致病性菌株中SP突变相对普遍。因此，这项研究表明，SP中的突变在降低运输功能且不影响易位蛋白质的最终结构的同时，如何导致细胞外细胞器的功能获得，该细胞器结合了蛋白质以及生物适应性的整体适应性变化。

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