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空肠弯曲菌新型自转运蛋白和毒力因子 CapC

CapC, a Novel Autotransporter and Virulence Factor of Campylobacter jejuni.

机构信息

Department of Pathology and Infectious Diseases, School of Veterinary Medicine, University of Surrey, Guildford, United Kingdom

Department of Microbial Sciences, School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom.

出版信息

Appl Environ Microbiol. 2018 Aug 1;84(16). doi: 10.1128/AEM.01032-18. Print 2018 Aug 15.

Abstract

is recognized as an important causative agent of bacterial gastroenteritis in the developed world. Despite the identification of several factors contributing to infection, characterization of the virulence strategies employed by remains a significant challenge. Bacterial autotransporter proteins are a major class of secretory proteins in Gram-negative bacteria, and notably, many autotransporter proteins contribute to bacterial virulence. The aim of this study was to characterize the 81116 C8J_1278 gene (), predicted to encode an autotransporter protein, and examine the contribution of this factor to virulence of The predicted CapC protein has a number of features that are consistent with autotransporters, including the N-terminal signal sequence and the C-terminal β-barrel domain and was determined to localize to the outer membrane. Inactivation of the gene in 81116 and M1 resulted in reduced insecticidal activity in larvae. Furthermore, mutants displayed significantly reduced adherence to and invasion of nonpolarized, partially differentiated Caco-2 and T84 intestinal epithelial cells. Gentamicin treatment showed that the reduced invasion of the mutant is primarily caused by reduced adherence to intestinal epithelial cells, not by reduced invasion capability. mutants caused reduced interleukin 8 (IL-8) secretion from intestinal epithelial cells and elicited a significantly diminished immune reaction in larvae, indicating that CapC functions as an immunogen. In conclusion, CapC is a new virulence determinant of that contributes to the integral infection process of adhesion to human intestinal epithelial cells. is a major causative agent of human gastroenteritis, making this zoonotic pathogen of significant importance to human and veterinary public health worldwide. The mechanisms by which interacts with intestinal epithelial cells and causes disease are still poorly understood due, in part, to the heterogeneity of infection biology. Given the importance of to public health, the need to characterize novel and existing virulence mechanisms is apparent. The significance of our research is in demonstrating the role of CapC, a novel virulence factor in that contributes to adhesion and invasion of the intestinal epithelium, thereby in part, addressing the dearth of knowledge concerning the factors involved in pathogenesis and the variation observed in the severity of human infection.

摘要

空肠弯曲菌被认为是发达国家细菌性肠胃炎的重要病原体。尽管已经确定了几种导致感染的因素,但空肠弯曲菌的毒力策略特征仍然是一个重大挑战。细菌自转运蛋白是革兰氏阴性菌中主要的一类分泌蛋白,值得注意的是,许多自转运蛋白有助于细菌的毒力。本研究的目的是对 81116 C8J_1278 基因()进行特征描述,该基因预测编码一种自转运蛋白,并研究该因子对空肠弯曲菌毒力的贡献。预测的 CapC 蛋白具有许多与自转运蛋白一致的特征,包括 N 端信号序列和 C 端 β-桶结构域,并被确定定位于外膜。在 81116 和 M1 中基因的失活导致幼虫的杀虫活性降低。此外,突变体对非极化、部分分化的 Caco-2 和 T84 肠上皮细胞的粘附和侵袭能力显著降低。庆大霉素处理表明,突变体侵袭能力降低主要是由于对肠上皮细胞的粘附减少,而不是由于侵袭能力降低。突变体导致肠上皮细胞分泌的白细胞介素 8(IL-8)减少,并在幼虫中引起免疫反应明显减弱,表明 CapC 作为免疫原发挥作用。总之,CapC 是空肠弯曲菌的一个新的毒力决定因素,有助于其与人类肠上皮细胞的完整感染过程。空肠弯曲菌是人类肠胃炎的主要病原体,使这种人畜共患病病原体对全球人类和兽医公共卫生具有重要意义。由于空肠弯曲菌感染生物学的异质性,空肠弯曲菌与肠上皮细胞相互作用并引起疾病的机制仍知之甚少。鉴于空肠弯曲菌对公共卫生的重要性,需要对新的和现有的毒力机制进行特征描述。我们研究的意义在于证明 CapC 的作用,CapC 是空肠弯曲菌的一个新的毒力因子,有助于肠上皮细胞的粘附和侵袭,从而部分解决了参与空肠弯曲菌发病机制的因素以及人类感染严重程度的差异的知识匮乏问题。

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