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Vat-AIEC 蛋白酶促进与克罗恩病相关的大肠杆菌穿过肠道黏液层。

The Vat-AIEC protease promotes crossing of the intestinal mucus layer by Crohn's disease-associated Escherichia coli.

机构信息

Laboratoire de Bactériologie, Centre Hospitalo-Universitaire Clermont-Ferrand, Clermont-Ferrand, France.

Microbes, Intestins, Inflammation et Susceptibilité de l'Hôte, Université d'Auvergne, INSERM U1071, INRA USC2018, Clermont-Ferrand, France.

出版信息

Cell Microbiol. 2016 May;18(5):617-31. doi: 10.1111/cmi.12539. Epub 2015 Nov 23.

Abstract

The aetiology of Crohn's disease (CD) involves disorders in host genetic factors and intestinal microbiota. Adherent-invasive Escherichia coli (AIEC) are receiving increased attention because in studies of mucosa-associated microbiota, they are more prevalent in CD patients than in healthy subjects. AIEC are associated both with ileal and colonic disease phenotypes. In this study, we reported a protease called Vat-AIEC from AIEC that favours the mucosa colonization. The deletion of the Vat-AIEC-encoding gene resulted in an adhesion-impaired phenotype in vitro and affected the colonization of bacteria in contact with intestinal epithelial cells in a murine intestinal loop model, and also their gut colonization in vivo. Furthermore, unlike LF82Δvat-AIEC, wild-type AIEC reference strain LF82 was able to penetrate a mucus column extensively and promoted the degradation of mucins and a decrease in mucus viscosity. Vat-AIEC transcription was stimulated by several chemical conditions found in the ileum environment. Finally, the screening of E. coli strains isolated from CD patients revealed a preferential vat-AIEC association with AIEC strains belonging to the B2 phylogroup. Overall, this study revealed a new component of AIEC virulence that might favour their implantation in the gut of CD patients.

摘要

克罗恩病(CD)的病因涉及宿主遗传因素和肠道微生物群的紊乱。黏附侵袭性大肠杆菌(AIEC)越来越受到关注,因为在黏膜相关微生物群的研究中,它们在 CD 患者中的流行程度高于健康受试者。AIEC 与回肠和结肠疾病表型都有关。在这项研究中,我们报道了一种来自 AIEC 的名为 Vat-AIEC 的蛋白酶,它有利于黏膜定植。Vat-AIEC 编码基因的缺失导致体外黏附受损表型,并影响细菌在肠道上皮细胞接触的小鼠肠道环模型中的定植,也影响其体内肠道定植。此外,与 LF82Δvat-AIEC 不同,野生型 AIEC 参考株 LF82 能够广泛穿透黏液柱,并促进黏蛋白的降解和黏液粘度的降低。Vat-AIEC 的转录受到回肠环境中发现的几种化学条件的刺激。最后,对从 CD 患者中分离出的大肠杆菌菌株的筛选显示,vat-AIEC 与属于 B2 进化枝的 AIEC 菌株的关联更为密切。总的来说,这项研究揭示了 AIEC 毒力的一个新成分,可能有利于它们在 CD 患者肠道中的定植。

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