Abstract
Rifaximin is a semi-synthetic rifamycin derivative that is used to treat different conditions including bacterial diarrhea and hepatic encephalopathy. Rifaximin is of particular interest because it is poorly adsorbed in the intestines and has minimal effect on colonic microflora. We previously demonstrated that rifaximin affected epithelial cell physiology by altering infectivity by enteric pathogens and baseline inflammation suggesting that rifaximin conferred cytoprotection against colonization and infection. Effects of rifaximin on epithelial cells were further examined by comparing the protein expression profile of cells pretreated with rifaximin, rifampin (control antibiotic), or media (untreated). Two-dimensional (2-D) gel electrophoresis identified 36 protein spots that were up- or down-regulated by over 1.7-fold in rifaximin treated cells compared to controls. 15 of these spots were down-regulated, including annexin A5, intestinal-type alkaline phosphatase, histone H4, and histone-binding protein RbbP4. 21 spots were up-regulated, including heat shock protein (HSP) 90α and fascin. Many of the identified proteins are associated with cell structure and cytoskeleton, transcription and translation, and cellular metabolism. These data suggested that in addition to its antimicrobial properties, rifaximin may alter host cell physiology that provides cytoprotective effects against bacterial pathogens.
Highlights
Rifaximin is a semi-synthetic, poorly-absorbed (,0.4%) rifamycin derivative used to treat travelers’ diarrhea due to bacterial enteropathogens and hepatic encephalopathy (HE) [1,2,3,4,5,6]
We previously demonstrated that pretreatment of the HEp-2 epithelial cell line with rifaximin significantly reduced the ability of enteroaggregative Escherichia coli (EAEC) to adhere to either the epithelial cells or glass slides compared to untreated cells or cells treated with the related antibiotic rifampin [14]
Comparison of the 2-D gel profile of HEp-2 cells treated with rifaximin relative to the profiles defined for HEp-2 cells in each of the respective control groups identified 184 polypeptide spots differentially up- or down-regulated, only 36 spots were selected for sequencing based on their differential expression levels
Summary
Rifaximin is a semi-synthetic, poorly-absorbed (,0.4%) rifamycin derivative used to treat travelers’ diarrhea due to bacterial enteropathogens and hepatic encephalopathy (HE) [1,2,3,4,5,6]. We previously demonstrated that pretreatment of the HEp-2 epithelial cell line with rifaximin significantly reduced the ability of enteroaggregative Escherichia coli (EAEC) to adhere to either the epithelial cells or glass slides compared to untreated cells or cells treated with the related antibiotic rifampin [14]. Rifaximin pretreatment of HEp-2 cells reduced Bacillus anthracis internalization into lung epithelial cells (A549) but had no effect on Shigella sonnei internalization into cervical epithelial (HeLa) cells. These data suggested that rifaximin induced changes to supernatant cytokine profiles and interfered with the cellular process utilized by some pathogens (EAEC and B. anthracis) but not others (S. sonnei) that use a type III secretory system to gain access to the intracellular compartment [14]
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