AAC Accepts, published online ahead of print on 26 October 2009

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Antimicrob. Agents Chemother. doi:10.1128/AAC.00691-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Pretreatment of Epithelial Cells with Rifaximin Alters Bacterial Attachment and Internalization Profiles

Eric L. Brown^*, Qiong Xue, Zhi-Dong Jiang, Yi Xu, and Herbert L. DuPont

The University of Texas School of Public Health, Center for Infectious Diseases, St. Luke's Episcopal Hospital and Baylor College of Medicine, Houston, TX; Texas A&M Health Science Center, Institute of Biosciences and Technology, Center for Infectious and Inflammatory Diseases, Houston, TX

^* To whom correspondence should be addressed. Email: eric.l.brown{at}uth.tmc.edu.

Rifaximin is a poorly absorbed semi-synthetic antibiotic derivative of rifampin licensed for use in the treatment of traveler's diarrhea. Rifaximin reduces symptoms of enteric infection, often without pathogen eradication and with limited effects on intestinal flora. Epithelia cells (HEp-2, larynx; HCT-8, ileocecal; A549, lung and HeLa, cervical) were pretreated with rifaximin (or control antibiotics) prior to the addition of enteroaggregative Echerichia coli (EAEC). EAEC adherence was significantly reduced following rifaximin pretreatment compared to pretreatment with rifampin or doxycycline for 3 of 4 cell lines tested. The rifaximin-mediated changes to epithelial cells were explored further by testing attachment and internalization of either Bacillus anthracis or Shigella sonnei to A549 or Hela cells, respectively. Attachment and internalization of B. anthracis was significantly reduced following rifaximin pretreatment. In contrast, neither attachment nor internalization of S. sonnei were affected by rifaximin pretreatment of HeLa cells, suggesting that rifaximin-mediated modulation of host cell physiology affected bacteria that utilize distinct attachment/internalization mechanism 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.