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高黏液碳青霉烯耐药 ST25 感染人类肠道上皮细胞并诱导中度炎症。

Hypermucoviscous Carbapenem-Resistant ST25 Infect Human Intestinal Epithelial Cells and Induce Moderate Inflammation.

机构信息

Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman 4000, Argentina.

Laboratory of Antimicrobials, Institute of Microbiology "Luis C. Verna", Faculty of Biochemistry, Chemistry and Pharmacy, National University of Tucuman, Tucuman 4000, Argentina.

出版信息

Int J Mol Sci. 2023 May 15;24(10):8804. doi: 10.3390/ijms24108804.

Abstract

is an opportunistic pathogen that can produce moderate and severe infections in immunosuppressed hosts. In recent years, an increase in the isolation of hypermucoviscous carbapenem-resistant with sequence type 25 (ST25) in hospitals in Norwest Argentina was observed. This work aimed to study the virulence and inflammatory potential of two ST25 strains (LABACER01 and LABACER27) in the intestinal mucosa. The human intestinal Caco-2 cells were infected with the ST25 strains, and their adhesion and invasion rates and changes in the expression of tight junction and inflammatory factors genes were evaluated. ST25 strains were able to adhere and invade Caco-2 cells, reducing their viability. Furthermore, both strains reduced the expression of tight junction proteins (occludin, ZO-1, and claudin-5), altered permeability, and increased the expression of TGF-β and TLL1 and the inflammatory factors (COX-2, iNOS, MCP-1, IL-6, IL-8, and TNF-α) in Caco-2 cells. The inflammatory response induced by LABACER01 and LABACER27 was significantly lower than the one produced by LPS or other intestinal pathogens, including NTUH-K2044. No differences in virulence and inflammatory potential were found between LABACER01 and LABACER27. In line with these findings, no major differences between the strains were found when the comparative genomic analysis of virulence factors associated with intestinal infection/colonization was performed. This work is the first to demonstrate that hypermucoviscous carbapenem-resistant ST25 infects human intestinal epithelial cells and induces moderate inflammation.

摘要

是一种机会性病原体,能够在免疫抑制宿主中引起中度和重度感染。近年来,在阿根廷西北部的医院中观察到高黏液性耐碳青霉烯肠杆菌 ( )与序列型 25(ST25)的分离率增加。这项工作旨在研究两株 ST25 菌株(LABACER01 和 LABACER27)在肠黏膜中的毒力和炎症潜力。用 ST25 菌株感染人肠 Caco-2 细胞,评估其黏附和侵袭率以及紧密连接和炎症因子基因表达的变化。ST25 菌株能够黏附和侵袭 Caco-2 细胞,降低其活力。此外,两种菌株均降低了紧密连接蛋白(occludin、ZO-1 和 claudin-5)的表达,改变了通透性,并增加了 TGF-β 和 TLL1 以及炎症因子(COX-2、iNOS、MCP-1、IL-6、IL-8 和 TNF-α)在 Caco-2 细胞中的表达。LABACER01 和 LABACER27 诱导的炎症反应明显低于 LPS 或其他肠道病原体(包括 NTUH-K2044)产生的炎症反应。LABACER01 和 LABACER27 之间在毒力和炎症潜力方面没有发现差异。当对与肠道感染/定植相关的毒力因子进行比较基因组分析时,两种菌株之间没有发现明显的差异。这是首次证明高黏液性耐碳青霉烯肠杆菌 ST25 感染人肠上皮细胞并引起中度炎症的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86f9/10218288/3e145400726e/ijms-24-08804-g001.jpg

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