Dataset Information

Citrobacter rodentium ICC168 CPX SILAC

ABSTRACT: SILAC experiment to investigate proteome changes in response to the disruption of CPX in Citrobacter rodentium ICC168.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Citrobacter Rodentium Icc168

SUBMITTER: Nichollas Scott

LAB HEAD: Leonard J Foster

PROVIDER: PXD009049 | Pride | 2019-01-07

REPOSITORIES: Pride

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Publications

Characterization of the Citrobacter rodentium Cpx regulon and its role in host infection.

Vogt Stefanie L SL Scholz Roland R Peng Yun Y Guest Randi L RL Scott Nichollas E NE Woodward Sarah E SE Foster Leonard J LJ Raivio Tracy L TL Finlay B Brett BB

Molecular microbiology 20190211 3

Envelope-localized proteins, such as adhesins and secretion systems, play critical roles in host infection by Gram-negative pathogens. As such, their folding is monitored by envelope stress response systems. Previous studies demonstrated that the Cpx envelope stress response is required for virulence of Citrobacter rodentium, a murine pathogen used to model infections by the human pathogens enteropathogenic and enterohemorrhagic Escherichia coli; however, the mechanisms by which the Cpx response ...[more]

PMID: 30536519

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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.

Dataset Information

Citrobacter rodentium ICC168 CPX SILAC

Publications

Characterization of the Citrobacter rodentium Cpx regulon and its role in host infection.

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