Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Malaya Pirogovskaya 1a, 119435 Moscow, Russia.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Ulitsa Mikluho-Maklaya, 16/10, 117997 Moscow, Russia.
Int J Mol Sci. 2024 Sep 20;25(18):10118. doi: 10.3390/ijms251810118.
Adhesive-invasive has been suggested to be associated with the development of Crohn's disease (CD). It is assumed that they can provoke the onset of the inflammatory process as a result of the invasion of intestinal epithelial cells and then, due to survival inside macrophages and dendritic cells, stimulate chronic inflammation. In previous reports, we have shown that passage of the CD isolate ZvL2 on minimal medium M9 supplemented with sodium propionate (PA) as a carbon source stimulates and inhibits the adherent-invasive properties and the ability to survive in macrophages. This effect was reversible and not observed for the laboratory strain K12 MG1655. We were able to compare the isogenic strain AIEC in two phenotypes-virulent (ZvL2-PA) and non-virulent (ZvL2-GLU). Unlike ZvL2-GLU, ZvL2-PA activates the production of ROS and cytokines when interacting with neutrophils. The laboratory strain does not cause a similar effect. To activate neutrophils, bacterial opsonization is necessary. Differences in neutrophil NADH oxidase activation and ζ-potential for ZvL2-GLU and ZvL2-PA are associated with changes in membrane protein abundance, as demonstrated by differential 2D electrophoresis and LC-MS. The increase in ROS and cytokine production during the interaction of ZvL2-PA with neutrophils is associated with a rearrangement of the abundance of membrane proteins, which leads to the activation of Rcs and PhoP/Q signaling pathways and changes in the composition and/or modification of LPS. Certain isoforms of OmpA may play a role in the formation of the virulent phenotype of ZvL2-PA and participate in the activation of NADPH oxidase in neutrophils.
黏附侵袭性被认为与克罗恩病 (CD) 的发展有关。人们认为，它们可以通过侵袭肠上皮细胞引发炎症过程，然后由于在巨噬细胞和树突状细胞内存活而刺激慢性炎症。在之前的报告中，我们已经表明，将 CD 分离株 ZvL2 在补充有丙酸钠 (PA) 的最小培养基 M9 上传代作为碳源，可以刺激和抑制黏附侵袭特性和在巨噬细胞中存活的能力。这种效应是可逆的，在实验室菌株 K12 MG1655 中没有观察到。我们能够比较两种表型的同源菌株 AIEC——毒力型 (ZvL2-PA) 和非毒力型 (ZvL2-GLU)。与 ZvL2-GLU 不同，ZvL2-PA 在与中性粒细胞相互作用时会激活 ROS 和细胞因子的产生。实验室菌株不会产生类似的效果。要激活中性粒细胞，需要细菌调理。ZvL2-GLU 和 ZvL2-PA 的中性粒细胞 NADH 氧化酶激活和 ζ-电位的差异与膜蛋白丰度的变化有关，这通过差异 2D 电泳和 LC-MS 证明。ZvL2-PA 与中性粒细胞相互作用过程中 ROS 和细胞因子产生的增加与膜蛋白丰度的重新排列有关，这导致 Rcs 和 PhoP/Q 信号通路的激活以及 LPS 的组成和/或修饰的变化。OmpA 的某些同工型可能在 ZvL2-PA 毒力表型的形成中起作用，并参与中性粒细胞 NADPH 氧化酶的激活。
