Intestinal translocation of enterococci requires a threshold level of enterococcal overgrowth in the lumen (original) (raw)

Rigottier-Gois & pascale serror enterococci are subdominant members of the human gastrointestinal microbiota. Enterococcus faecalis is generally harmless for healthy individuals, but it can cause a diverse range of infections in immunodeficient or elderly patients with severe underlying diseases. In this study, we analysed the levels of intestinal translocation of indigenous enterococci in C57BL/6, CF-1 and CX3CR1 −/− mice upon clindamycin antibiotic-induced dysbiosis. We found that C57BL/6 was the most permissive model for enterococcal translocation and that initiation of E. faecalis translocation coincided with a threshold of enterococcal colonisation in the gut lumen, which once reached, triggered E. faecalis dissemination to deeper organs. We showed that the extent to which E. faecalis clinical strain VE14821 competed with indigenous enterococci differed between the C57BL/6 and CX3CR1 −/− models. Finally, using a simplified gnotobiotic model, we observed E. faecalis crossing an intact intestinal tract using intestinal epithelial cells as one route to reach the lamina propria. Our study opens new perspectives for assessing the effect of various immunodeficiencies and for investigating mechanisms underlying enterococcal translocation. Enterococci are typical intestinal pathobionts. Although subdominant in the core intestinal microbiota and relatively harmless for healthy humans, under certain circumstances enterococci can cause infections such as bacteraemia, peritonitis, endocarditis, and urinary tract, wound, and device-related infections 1. The successful survival of enterococci in the hospital environment can be attributed to multidrug resistance and pathogenic traits. E. faecalis and E. faecium are the Enterococcus species most commonly associated with infection and vancomycin resistance. Enterococci are now ranked as the third most common type of nosocomial pathogen, with E. faecalis accounting for 60 to 80% of enterococcal infections 2,3. Despite increasing epidemiological evidence that intestinal domination by vancomycin-resistant enterococci (VRE) precedes human bloodstream infections 4-6 , it remains to be established whether E. faecalis blooming upon antibiotic treatment leads to translocation and subsequent human bloodstream infection. Pioneering work using mouse models highlighted the effect of antibiotic treatments on enterococcal colonisation and translocation 7,8. Enterococcal translocation has since been reported after antibiotic-induced dysbiosis, coinfection, severe inflammatory conditions, severe burn injuries and acute irradiation, and after disruption of intestinal mucosal barrier function in various mouse genetic backgrounds 8-16. Miyazaki et al. 10 showed that mice after treatment with antimicrobial agents and cyclophosphamide displayed increased susceptibility to VRE bacteraemia, leading to death in one-third of the mice following oral VRE inoculation. Amongst the 13 mouse lines tested under these conditions, C57BL/6 mice were identified as the strain most susceptible to VRE infection after oral inoculation. However, whether higher susceptibility of C57BL/6 mice correlates with a higher translocation efficiency remains to be established. Enterococcal translocation has also been investigated in some studies combining deficiency of mucosal immunity and intestinal dysbiosis 17,18. CX3CR1 −/− mice have been shown to display increased levels of bacterial translocation to the mesenteric lymph nodes, with Enterococcus being the predominant genus 18 .