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

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.

[1]  S. Turroni,et al.  Immunoregulatory activity of rifaximin associated with a resistant mutant of Bifidobacterium infantis. , 2009, International journal of antimicrobial agents.

[2]  G. Costamagna,et al.  Involvement of central immunity in uncomplicated diverticular disease , 2009, Scandinavian journal of gastroenterology.

[3]  T. Koehler,et al.  Potential dissemination of Bacillus anthracis utilizing human lung epithelial cells , 2008, Cellular microbiology.

[4]  A. Marchese,et al.  Effects of Rifaximin on Bacterial Virulence Mechanisms at Supra- and Sub-Inhibitory Concentrations , 2008, Journal of chemotherapy.

[5]  A. Fumi,et al.  Rifaximin Treatment for Symptoms of Irritable Bowel Syndrome , 2008, The Annals of pharmacotherapy.

[6]  H. Dupont,et al.  Virulence characteristics and the molecular epidemiology of enteroaggregative Escherichia coli isolates from travellers to developing countries. , 2007, Journal of medical microbiology.

[7]  D. Keene,et al.  Bacillus anthracis internalization by human fibroblasts and epithelial cells , 2007, Cellular microbiology.

[8]  P. Sansonetti,et al.  Shigella’s ways of manipulating the host intestinal innate and adaptive immune system: a tool box for survival? , 2007, Immunology and cell biology.

[9]  C. Leevy,et al.  Hospitalizations During the Use of Rifaximin Versus Lactulose for the Treatment of Hepatic Encephalopathy , 2007, Digestive Diseases and Sciences.

[10]  David N. Taylor,et al.  Rifaximin, a nonabsorbed oral antibiotic, prevents shigellosis after experimental challenge. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[11]  H. Dupont,et al.  Rifaximin: a novel nonabsorbed rifamycin for gastrointestinal disorders. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[12]  V. Ollivier,et al.  Interaction of Rifalazil with Oxidant-Generating Systems of Human Polymorphonuclear Neutrophils , 2005, Antimicrobial Agents and Chemotherapy.

[13]  H. Dupont,et al.  A Randomized, Double-Blind, Placebo-Controlled Trial of Rifaximin To Prevent Travelers' Diarrhea , 2005, Annals of Internal Medicine.

[14]  H. Dupont,et al.  Rifaximin: In vitro and in vivo Antibacterial Activity – A Review , 2005, Chemotherapy.

[15]  M. Labro.  Anti-inflammatory activity of ansamycins , 2005, Expert review of anti-infective therapy.

[16]  H. Dupont,et al.  Influence of rifaximin treatment on the susceptibility of intestinal Gram-negative flora and enterococci. , 2004, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[17]  H. Dupont,et al.  Interleukin-8 Response in an Intestinal HCT-8 Cell Line Infected with Enteroaggregative and Enterotoxigenic Escherichia coli , 2004, Clinical Diagnostic Laboratory Immunology.

[18]  Pascale Cossart,et al.  Bacterial Invasion: The Paradigms of Enteroinvasive Pathogens , 2004, Science.

[19]  D. Sack,et al.  Enteroaggregative Escherichia coli diarrhea in travelers: response to rifaximin therapy. , 2004, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[20]  B. Lowe,et al.  Therapy of travelers’ diarrhea with rifaximin on various continents , 2003, American Journal of Gastroenterology.

[21]  A. Federico,et al.  Cyclic treatment of chronic hepatic encephalopathy with rifaximin. Results of a double-blind clinical study. , 2003, Minerva gastroenterologica e dietologica.

[22]  E. Palazzini,et al.  In Vitro Activity and Fecal Concentration of Rifaximin after Oral Administration , 2000, Antimicrobial Agents and Chemotherapy.

[23]  M. Levine,et al.  Heterogeneity of enteroaggregative Escherichia coli virulence demonstrated in volunteers. , 1995, The Journal of infectious diseases.

[24]  C. B. Thorne,et al.  Demonstration of a capsule plasmid in Bacillus anthracis , 1985, Infection and immunity.

[25]  M. Pimentel,et al.  Rifaximin versus Other Antibiotics in the Primary Treatment and Retreatment of Bacterial Overgrowth in IBS , 2007, Digestive Diseases and Sciences.

[26]  H. Dupont,et al.  Rifaximin treatment of pathogen-negative travelers' diarrhea. , 2007, Journal of travel medicine.

[27]  J. Nataro,et al.  Methods for studying adhesion of diarrheagenic Escherichia coli. , 1995, Methods in enzymology.