Biomechanical and structural features of CS2 fimbriae of enterotoxigenic Escherichia coli.
Biomechanical and structural features of CS2 fimbriae of enterotoxigenic Escherichia coli.
复制标题
产肠毒素大肠杆菌CS2菌毛的生物力学和结构特征。
DOI：
10.1016/j.bpj.2015.05.022
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发表时间：
2015
影响因子：
3.4
通讯作者：
Andersson,Magnus
中科院分区：
文献类型：
--
作者：
Mortezaei,Narges;Singh,Bhupender;Zakrisson,Johan;Bullitt,Esther;Andersson,Magnus
产肠毒素大肠杆菌（ETEC）是全球腹泻的主要原因，在欠发达国家的儿童感染往往导致高死亡率。分离的ETEC表达过多的定殖因子（菌毛/皮利），其中CFA/I和CFA/II是最常见的，它们通过交替伴侣途径（ACP）组装。菌毛是丝状结构，其轴主要由螺旋排列的单个菌毛蛋白亚基组成，具有独特的生物力学能力，可以展开和倒带。在动态剪切力的不利条件下，持续的ETEC感染主要归因于ETEC菌毛的这种生物力学特征。最近的理解菌毛作为毒力因子的作用点，其结构和生物力学特征的进化适应。在这项工作中，我们研究了CFA/II组CS2菌毛的生物物理特性。其主要结构亚基科塔的同源建模揭示了与它们表达的生态位相关的结构线索。使用光镊力谱，我们发现CS2菌毛以10 pN的恒定力展开，并具有角速度（即，解绕所需的力随速度增加而呈指数上升的速度）为1300 nm/s。本工作中评估的CS2菌毛的生物物理特性将其与ETEC菌株表达的CFA/I和CS20菌毛一起归类为低力解旋菌毛组。这三种菌毛由ETEC表达，在相似的肠道环境中定殖，并表现出相似的生物物理特征，但其生物起源不同。我们的观察结果表明，环境对ETEC表达的菌毛的生物物理特性有很大影响。
EnterotoxigenicEscherichia coli(ETEC) are a major cause of diarrhea worldwide, and infection of children in under-developed countries often leads to high mortality rates. Isolated ETEC expresses a plethora of colonization factors (fimbriae/pili), of which CFA/I and CFA/II, which are assembled via the alternate chaperone pathway (ACP), are among the most common. Fimbriae are filamentous structures whose shafts are primarily composed of helically arranged single pilin-protein subunits, with a unique biomechanical ability to unwind and rewind. A sustained ETEC infection, under adverse conditions of dynamic shear forces, is primarily attributed to this biomechanical feature of ETEC fimbriae. Recent understanding about the role of fimbriae as virulence factors points to an evolutionary adaptation of their structural and biomechanical features. In this work, we investigated the biophysical properties of CS2 fimbriae from the CFA/II group. Homology modeling of its major structural subunit, CotA, reveals structural clues related to the niche in which they are expressed. Using optical-tweezers force spectroscopy, we found that CS2 fimbriae unwind at a constant force of 10 pN and have a corner velocity (i.e., the velocity at which the force required for unwinding rises exponentially with increased speed) of 1300 nm/s. The biophysical properties of CS2 fimbriae assessed in this work classify them into a low-force unwinding group of fimbriae together with the CFA/I and CS20 fimbriae expressed by ETEC strains. The three fimbriae are expressed by ETEC, colonize in similar gut environments, and exhibit similar biophysical features, but differ in their biogenesis. Our observation suggests that the environment has a strong impact on the biophysical characteristics of fimbriae expressed by ETEC.