Colonization of vancomycin-resistant Enterococcus faecium in human-derived colonic epithelium: Unraveling the transcriptional dynamics of host-enterococcal interactions

P. Stege, J. Beekman, Antoni P. A. Hendrickx, Laura van Eijk, Malbert R. C. Rogers, S. Suen, A. Vonk, Rob J. L. Willems, F. Paganelli
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Abstract

Enterococcus faecium is an opportunistic pathogen able to colonize the intestines of hospitalized patients. This initial colonization is an important step in the downstream pathogenesis, which includes outgrowth of the intestinal microbiota and potential infection of the host. The impact of intestinal overgrowth on host-enterococcal interactions is not well understood. We therefore applied a RNAseq approach in order to unravel the transcriptional dynamics of E. faecium upon co-culturing with human derived colonic epithelium. Co-cultures of colonic epithelium with a hospital-associated vancomycin resistant (vanA-type) E. faecium (VRE) showed that VRE resided on top of the colonic epithelium when analyzed by microscopy. RNAseq revealed that exposure to the colonic epithelium resulted in upregulation of 238 VRE genes compared to the control condition, including genes implicated in pili expression, conjugation (plasmid_2), genes related to sugar uptake and biofilm formation (chromossome). In total, 260 were downregulated including the vanA operon located on plasmid_3. Pathway analysis revealed an overall switch in metabolism to amino acid scavenging and reduction. In summary, our study demonstrates that co-culturing of VRE with human colonic epithelium promotes an elaborate gene response in VRE, enhancing our insight in host-E. faecium interactions, which might facilitate the design of novel anti-infectivity strategies.
耐万古霉素肠球菌在人源结肠上皮细胞中的定植:揭示宿主与肠球菌相互作用的转录动态
粪肠球菌是一种机会性病原体,能够在住院患者的肠道中定植。最初的定植是下游发病机制的重要一步,包括肠道微生物群的生长和宿主的潜在感染。肠道过度生长对宿主与肠球菌相互作用的影响尚不十分清楚。因此,我们采用 RNAseq 方法来揭示粪肠球菌与人类结肠上皮共培养时的转录动态。将结肠上皮与医院相关的耐万古霉素(vanA 型)粪大肠杆菌(VRE)共培养后,显微镜分析显示 VRE 位于结肠上皮的顶部。RNAseq 结果显示,与对照组相比,暴露于结肠上皮导致 238 个 VRE 基因上调,其中包括与纤毛表达、连接(质粒_2)、糖摄取和生物膜形成(染色体组)相关的基因。总共有 260 个基因被下调,其中包括位于质粒_3 上的 vanA 操作子。通路分析表明,新陈代谢总体上转向氨基酸清除和还原。总之,我们的研究表明,将 VRE 与人类结肠上皮细胞共培养可促进 VRE 中复杂的基因反应,从而提高我们对宿主与粪肠杆菌相互作用的洞察力,这可能有助于设计新型抗感染策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
3.30
自引率
0.00%
发文量
0
审稿时长
15 weeks
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