Pobeguts Olga V, Ladygina Valentina G, Evsyutina Daria V, Eremeev Artem V, Zubov Aleksandr I, Matyushkina Daria S, Scherbakov Peter L, Rakitina Daria V, Fisunov Gleb Y
Department of Molecular Biology and Genetics, Federal Research and Clinical Centre of Physical and Chemical Medicine, Federal Medical-Biological Agency, Moscow, Russia.
A. S. Loginov Moscow Clinical Scientific Center, Moscow, Russia.
Front Microbiol. 2020 Jul 8;11:1460. doi: 10.3389/fmicb.2020.01460. eCollection 2020.
Crohn's disease (CD) is a severe chronic immune-mediated granulomatous inflammatory disease of the gastrointestinal tract. The mechanisms of CD pathogenesis remain obscure. Metagenomic analysis of samples from CD patients revealed that several of them have the elevated level of with adhesive-invasive phenotype (AIEC). Previously, we isolated an strain CD isolate ZvL2 from a patient with CD, which features AIEC phenotype. Here, we demonstrate that prolonged growth on propionate containing medium stimulates virulent properties of CD isolate ZvL2, while prolonged growth on glucose reduces these properties to levels indistinguishable from laboratory strain K-12 MG1655. Propionate presence also boosts the ability of CD isolate ZvL2 to penetrate and colonize macrophages. The effect of propionate is reversible, re-passaging of CD isolate on M9 medium supplemented with glucose leads to the loss of its virulent properties. Proteome analysis of CD isolate ZvL2 growth in medium supplemented with propionate or glucose revealed that propionate induces expression porins OmpA and OmpW, transcription factors and , and universal stress protein , which were previously found to be important for macrophage colonization by enteropathogenic bacteria.
克罗恩病（CD）是一种严重的慢性免疫介导的胃肠道肉芽肿性炎症性疾病。CD发病机制仍不清楚。对CD患者样本的宏基因组分析显示，其中一些患者具有黏附侵袭性表型（AIEC）的水平升高。此前，我们从一名CD患者中分离出一株CD分离株ZvL2，其具有AIEC表型。在此，我们证明在含丙酸盐的培养基上长时间生长会刺激CD分离株ZvL2的毒力特性，而在葡萄糖上长时间生长会将这些特性降低到与实验室菌株K-12 MG1655无法区分的水平。丙酸盐的存在还增强了CD分离株ZvL2穿透和定殖巨噬细胞的能力。丙酸盐的作用是可逆的，将CD分离株在补充葡萄糖的M9培养基上再次传代培养会导致其毒力特性丧失。对在补充有丙酸盐或葡萄糖的培养基中生长的CD分离株ZvL2进行蛋白质组分析发现，丙酸盐诱导孔蛋白OmpA和OmpW、转录因子以及普遍应激蛋白的表达，这些蛋白先前被发现对肠道病原菌定殖巨噬细胞很重要。
