Cell:霍乱弧菌仅需改变形状就可提高感染力

2017-01-15 不详 生物谷

根据一项新的研究,来自美国普林斯顿大学、斯坦福大学、印第安纳大学和中国南京农业大学的研究人员发现导致危及生命的霍乱疾病的细菌可能通过协调一波大规模的形状改变而允许它们更加有效地侵入它们的不知情受害者的肠道,从而引发感染。 研究人员发现允许霍乱弧菌变成弯曲形状的蛋白,这种弯曲形状很可能允许这种细菌发生扭摆,随后逃进肠道内壁的保护性粘膜中。他们报道改变形状的蛋白---他们命名为CrvA---



根据一项新的研究,来自美国普林斯顿大学、斯坦福大学、印第安纳大学和中国南京农业大学的研究人员发现导致危及生命的霍乱疾病的细菌可能通过协调一波大规模的形状改变而允许它们更加有效地侵入它们的不知情受害者的肠道,从而引发感染。

研究人员发现允许霍乱弧菌变成弯曲形状的蛋白,这种弯曲形状很可能允许这种细菌发生扭摆,随后逃进肠道内壁的保护性粘膜中。他们报道改变形状的蛋白---他们命名为CrvA---的表达是通过群体感应(quorum sensing)过程而被激活的。在这个过程中,细菌彼此之间相互沟通,协同感染。相关研究结果发表在2017年1月12日那期Cell期刊上,论文标题为“A Periplasmic Polymer Curves Vibrio cholerae and Promotes Pathogenesis”。

在实验中,研究人员发现弯曲的霍乱弧菌细胞能够更加容易地在厚厚的凝胶中迁移。另一方面,他们的研究也表明直杆状的霍乱弧菌不能那么有效地感染宿主。

论文通信作者、普林斯顿大学分子生物学教授Zemer Gitai说,如果形状在霍乱弧菌感染中发挥着关键性的作用,那么人们就可能能够开发阻止这种细菌改变形状的能力或者改变病人的肠道从而让这种细菌不能够感染它的霍乱疗法。每年,全世界上百万人患上霍乱,导致上***死亡(主要是死于脱水)。在清洁的水源比较稀缺的地方,如发展中国家、战区和受到自然灾难影响的区域,霍乱尤为猖獗。

Gitai说,“我们知道如果霍乱弧菌不能够弯曲的话,那么它就不能够让动物患病。这提示着如果我们能够阻止它们发生弯曲的话,那么这就会限制它们让人们患病的能力。它是如何做到这一点的仍然需要人们去解决。”

这项研究发现CrvA蛋白丝在霍乱弧菌的一边上组装,形成一种硬的聚合物,从而阻止这种细菌在这一边上的生长。这种细菌的另一边生长得更快,从而导致弯曲的形状。研究人员发现CrvA表达是通过群体感应激活的,因此,当细菌群体密度增加时,它的表达也会增加。这种细菌利用群体感应在彼此之间发出警报:它们的环境已由水---在那里,有利于杆状形状形成---改变为宿主肠道。

论文第一作者、Gitai研究团队研究生Thomas Bartlett说,总体而言,这些发现提示着细菌导致的疾病可能主要取决于这种细菌本身的生理学特征和它们与环境之间的相互作用。他说,比如,所有弯曲的弧菌属细菌物种(包括在未煮熟的海鲜食物中发现的能够导致严重疾病的创伤弧菌)都表达蛋白CrvA。

Bartlett说,细菌进化出特定的性状以便在它们理想的环境(比如肠道)中存活下来。Gitai团队在2014年发表的一项研究已发现良性细菌新月柄杆菌(Caulobacter crescentus)的神秘弯曲形状有助它们更好地抵抗它们生长的湖泊、池塘和溪水中的水流。

Bartlett说,“霍乱弧菌和新月柄杆菌存在足够大的不同以至于它们看起来是独立进化的,但是它们实际上是非常相似的。在这两种细菌中,它们的弯曲形状允许它们处理它们生活的环境的流体力学性质。”

显著的是,研究人员发现CrvA位于周质(periplasm)--在霍乱弧菌等革兰氏阴性菌外膜和内膜之间的一个细胞区室---中。尽管细菌利用其它的蛋白丝呈现出多种形状,但是CrvA首个在周质中发现的具有这种功能的蛋白丝。从治疗角度而言,周质要比细菌的内部(即细胞质)更容易接近。

在这项研究中,研究人员开发出一种被称作小囊结构重塑定量分析(Quantitative Analysis of Sacculus Architecture Remodeling, QuASAR)的计算机程序来理解在周质的狭小空间中CrvA如何发挥功能。

原始出处:


Thomas M. Bartlett, Benjamin P. Bratton, Amit Duvshani, Amanda Miguel, Ying Sheng, Nicholas R. Martin, Jeffrey P. Nguyen, Alexandre Persat8, Samantha M. Desmarais, Michael S. VanNieuwenhze, Kerwyn Casey Huang, Jun Zhu, Joshua W. Shaevitz, Zemer Gitai.A Periplasmic Polymer Curves Vibrio cholerae and Promotes Pathogenesis.Cell doi:10.1016/j.cell.2016.12.019


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    2017-10-14 维他命
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    2017-01-17 klivis
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    2017-01-16 ylzr123

    研究人员发现允许霍乱弧菌变成弯曲形状的蛋白,这种弯曲形状很可能允许这种细菌发生扭摆,随后逃进肠道内壁的保护性粘膜中。

    0

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