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Evaluation of Protein–Protein Interactions using an On-Membrane Digestion Technique
Published on: July 19, 2019
Rifaximin-mediated changes to the epithelial cell proteome: 2-D gel analysis
Caroline Schrodt1, Erin E McHugh, Mary Ann Gawinowicz
1Center for Infectious Diseases, the University of Texas School of Public Health, Houston, Texas, United States of America.
Plos One
|August 8, 2013
Summary
Rifaximin, an antibiotic, alters host cell protein expression, enhancing cytoprotection against bacterial pathogens. This suggests non-antimicrobial mechanisms contribute to its therapeutic effects in conditions like hepatic encephalopathy.
Area of Science:
- Gastroenterology
- Microbiology
- Cellular Biology
Background:
- Rifaximin is a poorly absorbed antibiotic used for bacterial diarrhea and hepatic encephalopathy.
- Previous studies indicated rifaximin affects epithelial cell physiology and confers cytoprotection.
- The precise mechanisms underlying these cytoprotective effects require further investigation.
Purpose of the Study:
- To investigate the effects of rifaximin on the protein expression profile of epithelial cells.
- To identify specific proteins modulated by rifaximin treatment.
- To understand how rifaximin's impact on host cell physiology contributes to its therapeutic actions.
Main Methods:
- Comparison of protein expression profiles in epithelial cells pretreated with rifaximin, rifampin (control), or media.
- Utilized two-dimensional (2-D) gel electrophoresis to identify differentially expressed proteins.
- Quantitative analysis of protein spot up-regulation and down-regulation.
Main Results:
- Rifaximin treatment altered the expression of 36 protein spots by over 1.7-fold compared to controls.
- Down-regulated proteins included annexin A5, intestinal-type alkaline phosphatase, histone H4, and RbbP4.
- Up-regulated proteins included heat shock protein (HSP) 90α and fascin.
- Affected proteins were associated with cell structure, transcription, translation, and metabolism.
Conclusions:
- Rifaximin modulates host epithelial cell protein expression beyond its antimicrobial activity.
- These protein alterations suggest rifaximin confers cytoprotective effects through host-directed mechanisms.
- Findings support the hypothesis that rifaximin's therapeutic benefits involve both antimicrobial and host cell-modulating properties.
