Department of Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou 310058, China; Department of Laboratory Medicine, Wuxi Fifth People's Hospital, Wuxi 214005, China.
Department of Laboratory Medicine, Wuxi Fifth People's Hospital, Wuxi 214005, China.
Int J Med Microbiol. 2022 Aug;312(6):151561. doi: 10.1016/j.ijmm.2022.151561. Epub 2022 Sep 2.
Klebsiella pneumoniae is a gram-negative bacterium that can cause many diseases in hospitals and communities. Intestinal K. pneumoniae infections are relatively rare. Most K. pneumoniae infections begin with the colonization of the gastrointestinal system. In this study, clinically isolated K. pneumoniae strains were used to infect intestinal epithelial Caco-2 cells to study the possible intestinal translocation mechanism of K. pneumoniae. We found that of the three K. pneumoniae strains tested, KP1821 exhibited the strongest adhesive and invasive abilities and that the adhesion to Caco-2 intestinal epithelial cells was affected by the acidic environment of the stomach. Transcriptome sequencing revealed the involvement of molecules associated with the extracellular matrix and cell adhesion, inflammatory response, calcium ion and transforming growth factor β (TGF-β) signaling pathways, and other abnormalities in biological processes and cell signaling pathways. Additionally, tolloid-like protein 1 (TLL1) was significantly upregulated. Knocking down TLL1 with shRNA significantly reduced KP1821's ability to invade and adhere to intestinal epithelial cells. TLL1 is involved in the activation of the TGF-β signaling pathway. Inhibition of this pathway using the inhibitor SB431542 induced significantly reduced adhesion and invasion capabilities of KP1821. Our findings demonstrate that TLL1 participates in K. pneumoniae adhesion and invasion of intestinal epithelial cells by activating the TGF-β signaling pathway.
肺炎克雷伯菌是一种革兰氏阴性菌，可在医院和社区引起许多疾病。肠道肺炎克雷伯菌感染相对较少。大多数肺炎克雷伯菌感染始于胃肠道系统的定植。在这项研究中，我们使用临床分离的肺炎克雷伯菌菌株感染肠道上皮细胞 Caco-2，以研究肺炎克雷伯菌可能的肠道易位机制。我们发现，在所测试的三种肺炎克雷伯菌菌株中，KP1821 表现出最强的粘附和侵袭能力，并且对 Caco-2 肠道上皮细胞的粘附受胃内酸性环境的影响。转录组测序揭示了与细胞外基质和细胞粘附、炎症反应、钙离子和转化生长因子β（TGF-β）信号通路相关的分子以及生物过程和细胞信号通路中的其他异常的参与。此外，Toll 样蛋白 1（TLL1）显著上调。用 shRNA 敲低 TLL1 显著降低了 KP1821 侵袭和粘附肠道上皮细胞的能力。TLL1 参与 TGF-β 信号通路的激活。使用抑制剂 SB431542 抑制该通路可显著降低 KP1821 的粘附和侵袭能力。我们的研究结果表明，TLL1 通过激活 TGF-β 信号通路参与肺炎克雷伯菌对肠道上皮细胞的粘附和侵袭。
