Dataset Information

Effect of Dhps deletion and Citrobacter rodentium on the proteome of colonic epithelial cells

ABSTRACT: Dhps mice and Dhps;Vil1 mice were infected or not with Citrobacter rodentium (10^9 bacteria/mouse) for 14 days, and cell lysates were prepared for analysis. A total of 4 mice per group were used for the following groups: (1) Vil1<+> no C. Rod; (2) Vil1 no C. Rod; (3) Vil1<+> with C. Rod; (4) Vil1 with C. Rod

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Colonic Epithelial Cell, Colon Epithelial Cell

DISEASE(S): Bacterial Infectious Disease,Colitis

SUBMITTER: Kristie Lindsey Rose

LAB HEAD: Kristie Lindsey Rose

PROVIDER: PXD051536 | Pride | 2025-05-06

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	6406_20240306_mq_evidence.txt	Txt
	6406_20240306_mq_msstats_4.8.7_report_04_2024.xlsx	Xlsx
	6406_20240306_mq_peptides.txt	Txt
	6406_20240306_mq_proteinGroups.txt	Txt
	pEX1_ml_6406_20240213_CR_1_1uL_1.raw	Raw

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Publications

Hypusination in intestinal epithelial cells protects mice from infectious colitis.

Gobert Alain P AP Hawkins Caroline V CV Williams Kamery J KJ Snyder Lydia A LA Barry Daniel P DP Asim Mohammad M Allaman Margaret M MM McNamara Kara M KM Delgado Alberto G AG Wang Yu Y Zhao Shilin S Rose Kristie L KL Piazuelo M Blanca MB Wilson Keith T KT

Gut microbes 20240101 1

Enteropathogenic <i>Escherichia coli</i> (EPEC) is a bacterium that causes attaching/effacing (A/E) lesions and serious diarrheal disease, a major health issue in developing countries. EPEC pathogenicity results from the effect of virulence factors and dysregulation of host responses. Polyamines, including spermidine, play a major role in intestinal homeostasis. Spermidine is the substrate for deoxyhypusine synthase (DHPS), which catalyzes the conjugation of the amino acid hypusine to eukaryotic ...[more]

PMID: 39673545

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Project description:Opioids analgesics are frequently prescribed in the United States and worldwide. However, serious side effects such as addiction, immunosuppression and gastrointestinal symptoms limit their use. It has been recently demonstrated that morphine treatment results in significant disruption in gut barrier function leading to increased translocation of gut commensal bacteria. Further study indicated distinct alterations in the gut microbiome and metabolome following morphine treatment, contributing to the negative consequences associated with opioid use. However, it is unclear how opioids modulate gut homeostasis in the context of a hospital acquired bacterial infection. In the current study, a mouse model of C. rodentium infection was used to investigate the role of morphine in the modulation of gut homeostasis in the context of a hospital acquired bacterial infection. Citrobacter rodentium is a natural mouse pathogen that models intestinal infection by enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) and causes attaching and effacing lesions and colonic hyperplasia. Morphine treatment resulted in 1) the promotion of C. rodentium systemic dissemination, 2) increase in virulence factors expression with C. rodentium colonization in intestinal contents, 3) altered gut microbiome, 4) damaged integrity of gut epithelial barrier function, 5) inhibition of C. rodentium-induced increase in goblet cells, and 6) dysregulated IL-17A immune response. This is the first study to demonstrate that morphine promotes pathogen dissemination in the context of intestinal C. rodentium infection, indicating morphine modulates virulence factor-mediated adhesion of pathogenic bacteria and induces disruption of mucosal host defense during C. rodentium intestinal infection in mice. This study demonstrates and further validates a positive correlation between opioid drug use/abuse and increased risk of infections, suggesting over-prescription of opioids may increase the risk in the emergence of pathogenic strains and should be used cautiously. Therapeutics directed at maintaining gut homeostasis during opioid use may reduce the comorbidities associated with opioid use for pain management.