Brown EL, Xue Q, Jiang ZD, Xu Y, Dupont HL
Pretreatment of Epithelial Cells with Rifaximin Alters Bacterial Attachment and Internalization Profiles. [JOURNAL ARTICLE]
Antimicrob Agents Chemother 2009 Oct 26.
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.
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