Antibody-mediated disruption of the mechanics of CS20 fimbriae of enterotoxigenic Escherichia coli.
Antibody-mediated disruption of the mechanics of CS20 fimbriae of enterotoxigenic Escherichia coli.
复制标题
抗体介导的产肠毒素大肠杆菌 CS20 菌毛力学破坏。
DOI：
10.1038/srep13678
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发表时间：
2015
影响因子：
4.6
通讯作者：
Andersson,Magnus
中科院分区：
文献类型：
--
作者：
Singh,Bhupender;Mortezaei,Narges;Uhlin,BerntEric;Savarino,StephenJ;Bullitt,Esther;Andersson,Magnus
针对肠致病性大肠杆菌（ETEC）的预防性疫苗正在开发中，其中许多疫苗以常见的菌毛定植因子为主要成分，基于这些菌毛定植因子作为保护性抗原的经验证据。特别地，被动口服施用ETEC抗菌毛抗体预防ETEC腹泻。然而，关于肠内抗ETEC菌毛抗体预防疾病的具体机制知之甚少。使用大肠杆菌表面抗原20（CS20）菌毛作为模型ETEC定殖因子，我们使用力谱显示，抗菌毛抗体通过抑制其自然能力，以解开和倒带减少菌毛弹性。在抗CS20抗体的存在下，解开单个菌毛所需的力增加了几倍，延伸长度缩短了几倍。在抗CS20 Fab片段存在下的类似测量未显示任何作用，表明需要二价抗体结合以降低菌毛弹性。基于这些发现，我们提出了一种动物体内机制模型，即抗体介导的CS20菌毛生物力学特性的破坏阻碍了ETEC与肠粘膜表面的持续粘附。进一步阐明肠道抗体在机械破坏菌毛功能中所发挥的作用可能会提供与ETEC疫苗开发相关的见解。
Preventive vaccines against enterotoxigenicEscherichia coli(ETEC) are being developed, many of which target common fimbrial colonization factors as the major constituent, based on empirical evidence that these function as protective antigens. Particularly, passive oral administration of ETEC anti-fimbrial antibodies prevent ETEC diarrhea. Little is, however, known regarding the specific mechanisms by which intestinal antibodies against ETEC fimbriae function to prevent disease. Using coli surface antigen 20 (CS20) fimbriae as a model ETEC colonization factor, we show using force spectroscopy that anti-fimbrial antibodies diminish fimbrial elasticity by inhibiting their natural capacity to unwind and rewind. In the presence of anti-CS20 antibodies the force required to unwind a single fimbria was increased several-fold and the extension length was shortened several-fold. Similar measurements in the presence of anti-CS20 Fab fragments did not show any effect, indicating that bivalent antibody binding is required to reduce fimbrial elasticity. Based on these findings, we propose a model for anin-vivomechanism whereby antibody-mediated disruption of the biomechanical properties of CS20 fimbriae impedes sustained adhesion of ETEC to the intestinal mucosal surface. Further elucidation of the role played by intestinal antibodies in mechanical disruption of fimbrial function may provide insights relevant to ETEC vaccine development.