title: Assessment of the role of antibiotics and enterococcal virulence factors in a mouse model of extraintestinal translocation.
abstract: OBJECTIVE
  To study the relative contribution of antibiotics and bacterial virulence factors in the process of translocation of Enterococcus faecalis from the gut to extraintestinal organs.
  
  
  METHODS
  Prospective controlled animal study.
  
  
  METHODS
  Animal experimental laboratory at a university medical center.
  
  
  METHODS
  Fifty-two female Balb/c mice.
  
  
  METHODS
  We developed a mouse model to study the translocation of Enterococcus faecalis from the intestinal tract. Balb/c mice received sterile drinking water or antibiotic combinations to deplete their indigenous intestinal microflora. The animals subsequently were fed genetically engineered enterococci expressing different combinations of the putative enterococcal virulence factors aggregation substance and binding substance. Animals were killed, and their livers, spleens, and mesenteric lymph nodes were aseptically removed and cultured along with fecal samples for enumeration of bacteria.
  
  
  RESULTS
  All animals were colonized with the test strains at 2-6 x 109 colony forming units/g of feces; in the antibiotic-treated animals, feces were free from anaerobes and Enterobacteriaceae. In animals fed the identical bacterial mutant, the colony counts in mesenteric lymph nodes were significantly lower in mice not treated with antibiotics than in those treated with antibiotics (p =.016). Multigroup analysis of variance revealed no significant differences of the translocation frequencies for the different mutant strains; however, the differences were statistically significant for all groups receiving antibiotics vs. the group not receiving antibiotics (p <.05-.01). There was a trend (although not statistically significant) for a higher proportion of positive cultures from either spleen or liver in mice that had enterococci recovered from their mesenteric lymph nodes (28%) relative to those that did not have enterococci isolated from the lymph nodes (12%; rate ratio 2.39, p =.30 by logistic regression analysis).
  
  
  CONCLUSIONS
  Oral antibiotics can select for extraintestinal translocation of Enterococcus faecalis, and neither aggregation substance nor binding substance seems to be required for this process. The experiments encourage further exploration of host and microbial factors contributing to translocation and may provide a better understanding of the pathogenesis of enterococcal infections in patients in intensive care units.
authors.affiliation: Department of Anaesthesiology and Intensive Care, Tübingen University Hospital, Germany.
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Krueger
authors.forename: Soraya
authors.initials: S
authors.lastname: Krueger-Rameck
authors.forename: Stefanie
authors.initials: S
authors.lastname: Koch
authors.forename: Vincent
authors.initials: V
authors.lastname: Carey
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Pier
authors.forename: Johannes
authors.initials: J
authors.lastname: Huebner
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018988:Bacterial Translocation / Q000187:drug effects*; D013293:Enterococcus faecalis / Q000187:drug effects* / Q000472:pathogenicity*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D011446:Prospective Studies; D037521:Virulence Factors
chemical_list: D000900:Anti-Bacterial Agents; D037521:Virulence Factors