万古霉素耐药粪肠球菌对结肠癌细胞的致病性。
The pathogenicity of vancomycin-resistant Enterococcus faecalis to colon cancer cells.
机构信息
Department of Gastroenterology and Hepatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
出版信息
BMC Infect Dis. 2024 Feb 20;24(1):230. doi: 10.1186/s12879-024-09133-2.
BACKGROUND
The aim of this study was to investigate the pathogenicity of vancomycin-resistant Enterococcus faecalis (VREs) to human colon cells in vitro.
METHODS
Three E. faecalis isolates (2 VREs and E. faecalis ATCC 29212) were cocultured with NCM460, HT-29 and HCT116 cells. Changes in cell morphology and bacterial adhesion were assessed at different time points. Interleukin-8 (IL-8) and vascular endothelial growth factor A (VEGFA) expression were measured via RT-qPCR and enzyme-linked immunosorbent assay (ELISA), respectively. Cell migration and human umbilical vein endothelial cells (HUVECs) tube formation assays were used for angiogenesis studies. The activity of PI3K/AKT/mTOR signaling pathway was measured by Western blotting.
RESULTS
The growth and adhesion of E. faecalis at a multiplicity of infection (MOI) of 1:1 were greater than those at a MOI of 100:1(p < 0.05). Compared to E. faecalis ATCC 29212, VREs showed less invasive effect on NCM460 and HT-29 cells. E. faecalis promoted angiogenesis by secreting IL-8 and VEGFA in colon cells, and the cells infected with VREs produced more than those infected with the standard strain (p < 0.05). Additionally, the PI3K/AKT/mTOR signaling pathway was activated in E. faecalis infected cells, with VREs demonstrating a greater activation compared to E. faecalis ATCC 29212 (p < 0.05).
CONCLUSION
VREs contribute to the occurrence and development of CRC by promoting angiogenesis and activating the PI3K/AKT/mTOR signaling pathway.
背景
本研究旨在体外研究万古霉素耐药粪肠球菌（VRE）对人结肠细胞的致病性。
方法
将 3 株粪肠球菌分离株（2 株 VRE 和粪肠球菌 ATCC 29212）与 NCM460、HT-29 和 HCT116 细胞共培养。在不同时间点评估细胞形态和细菌黏附的变化。通过 RT-qPCR 和酶联免疫吸附试验（ELISA）分别测量白细胞介素 8（IL-8）和血管内皮生长因子 A（VEGFA）的表达。细胞迁移和人脐静脉内皮细胞（HUVEC）管形成试验用于血管生成研究。通过 Western blot 测定 PI3K/AKT/mTOR 信号通路的活性。
结果
在感染复数（MOI）为 1:1 时，粪肠球菌的生长和黏附作用大于 MOI 为 100:1 时（p<0.05）。与粪肠球菌 ATCC 29212 相比，VRE 对 NCM460 和 HT-29 细胞的侵袭作用较弱。粪肠球菌通过在结肠细胞中分泌 IL-8 和 VEGFA 促进血管生成，感染 VRE 的细胞比感染标准株的细胞产生的更多（p<0.05）。此外，PI3K/AKT/mTOR 信号通路在感染粪肠球菌的细胞中被激活，VRE 的激活程度大于粪肠球菌 ATCC 29212（p<0.05）。
结论
VRE 通过促进血管生成和激活 PI3K/AKT/mTOR 信号通路，促进 CRC 的发生和发展。
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