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Updated: Jun 19, 2026

Epithelial Cell Infection Analyses with Shigella
Published on: February 9, 2024
Pretreatment of epithelial cells with rifaximin alters bacterial attachment and internalization profiles
Eric L Brown1, Qiong Xue, Zhi-Dong Jiang
1The University of Texas School of Public Health, 1200 Herman Pressler, Houston, TX 77030, USA. eric.l.brown@uth.tmc.edu
Abstract:
Rifaximin is a poorly absorbed semisynthetic antibiotic derivative of rifampin licensed for use in the treatment of traveler's diarrhea. Rifaximin reduces the symptoms of enteric infection, often without pathogen eradication and with limited effects on intestinal flora. Epithelial cells (HEp-2 [laryngeal], HCT-8 [ileocecal], A549 [lung], and HeLa [cervical]) were pretreated with rifaximin (or control antibiotics) prior to the addition of enteroaggregative Escherichia coli (EAEC). EAEC adherence was significantly reduced following rifaximin pretreatment compared to pretreatment with rifampin or doxycycline for three of the four cell lines tested. The rifaximin-mediated changes to epithelial cells were explored further by testing the attachment and internalization of either Bacillus anthracis or Shigella sonnei into A549 or HeLa cells, respectively. The attachment and internalization of B. anthracis were significantly reduced following rifaximin pretreatment. In contrast, neither the attachment nor the internalization of S. sonnei was affected by rifaximin pretreatment of HeLa cells, suggesting that rifaximin-mediated modulation of host cell physiology affected bacteria utilizing distinct attachment/internalization mechanisms differently. In addition, rifaximin pretreatment of HEp-2 cells led to reduced concentrations of inflammatory cytokines from uninfected cells. The study provides evidence that rifaximin-mediated changes in epithelial cell physiology are associated with changes in bacterial attachment/internalization and reduced inflammatory cytokine release.
Insights
Rifaximin, an antibiotic for traveler's diarrhea, alters epithelial cells to reduce bacterial attachment and inflammatory responses. This mechanism impacts bacterial adhesion differently based on their specific mechanisms.
Area of Science:
- Microbiology
- Pharmacology
- Cell Biology
Background:
- Rifaximin is a poorly absorbed antibiotic used for traveler's diarrhea.
- It reduces enteric infection symptoms with limited impact on gut flora.
- Its effects on host-pathogen interactions are not fully understood.
Purpose of the Study:
- To investigate how rifaximin pretreatment affects bacterial adherence to epithelial cells.
- To explore rifaximin's influence on bacterial internalization into host cells.
- To determine if rifaximin modulates host cell inflammatory responses.
Main Methods:
- Epithelial cell lines (HEp-2, HCT-8, A549, HeLa) were pretreated with rifaximin.
- Pretreated cells were exposed to enteroaggregative Escherichia coli (EAEC), Bacillus anthracis, or Shigella sonnei.
- Bacterial attachment and internalization were quantified.
- Cytokine release from uninfected cells was measured.
Main Results:
- Rifaximin pretreatment significantly reduced EAEC adherence to three of four cell lines.
- Bacterial attachment and internalization of Bacillus anthracis were significantly reduced.
- Rifaximin did not affect attachment or internalization of Shigella sonnei.
- Rifaximin pretreatment reduced inflammatory cytokine release in HEp-2 cells.
Conclusions:
- Rifaximin alters epithelial cell physiology, impacting bacterial attachment and internalization.
- The effect of rifaximin varies depending on the bacteria's specific adhesion mechanisms.
- Rifaximin exhibits anti-inflammatory properties by reducing cytokine release from epithelial cells.
