Dual transcriptomic and proteomic analysis of intestinal epithelial cell response to Citrobacter rodentium infection in mice

Paradell Gil, Teresa 2024. Dual transcriptomic and proteomic analysis of intestinal epithelial cell response to Citrobacter rodentium infection in mice. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Citrobacter rodentium is a natural mouse pathogen and the etiological agent of transmissible murine colonic hyperplasia (CCH). As a member of the Attaching and Effacing (AE) pathogens, C. rodentium shares a similar infection strategy with Enteropathogenic Escherichia coli (EPEC) and Enterohemorrhagic E. coli (EHEC), two human pathogens responsible for diarrhoeal diseases that contribute significantly to morbidity and mortality worldwide. Since mice are resistant to EPEC and EHEC infections, C. rodentium provides an ideal surrogate model for in vivo studies to better understand the mechanisms of infection of AE pathogens. In this study, we aimed to elucidate the infection mechanisms of C. rodentium by investigating the transcriptome and proteome profiles of infected intestinal epithelial cells (IECs) in mice. Through the combined analysis of gene expression and protein patterns, we identified key regulatory pathways related to immune responses, inflammation, and metabolism. These included the upregulation of the pentose phosphate pathway, the ubiquitin-proteasome system, and the prostaglandin biosynthesis pathway. Additionally, the dual analysis demonstrated that the disruption of microvilli and mitochondria in infected IECs was due to the active destruction of these structures, as evidenced by a marked reduction in their protein levels, despite no changes being observed at the RNA levels. Additionally, we investigated the mRNA and protein targets of altered microRNA (miRNA) during C. rodentium infection. Our findings revealed no correlation between the miRNA levels, their corresponding mRNA targets, and the resulting protein levels. This lack of correlation suggests that the bacteria target the miRNA system potentially to promote disease progression. In summary, this research provides significant insights into the complex host-pathogen interactions during C. rodentium infection, contributing to a deeper understanding of similar AE pathogens such as EPEC and EHEC. This study enhances our understanding of infectious diseases by identifying crucial pathways that could be explored for diagnostic or therapeutic innovation.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Schools > Biosciences
Subjects:	Q Science > Q Science (General)
Date of First Compliant Deposit:	20 March 2025
Last Modified:	20 Mar 2025 15:05
URI:	https://orca.cardiff.ac.uk/id/eprint/177023

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