Surface protein Esp enhances pro-inflammatory cytokine expression through NF-κB activation during enterococcal infection.
Enterococcal surface protein (Esp) is encoded on a pathogenicity island in Enterococcus faecalis and E. faecium and is involved in biofilm formation and binding to epithelial cells. In this study, using Esp-expressing E. faecalis MMH594 and its isogenic Esp-deficient strain, as well as purified Esp, we show that Esp is sufficient for activation of NF-κB and the subsequent production of pro-inflammatory cytokines IL-1β and TNF-α in macrophages in vitro. In a mouse peritonitis model, we also show that mice infected with Esp-expressing E. faecalis showed comparatively higher levels of cytokines TNF-α, IL-1β and IL-6 in peritoneal fluid, and IL-6 in serum. Moreover, neutrophil infiltration and tissue damage in the liver was higher in the mice infected with the Esp-expressing strain compared with mice infected with the Esp-deficient mutant. These results add Esp to the growing list of enterococcal virulence factors that can modulate inflammation during infection and has implications for enterococcal pathogenesis.
Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Jun
J
Zou
Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA nathan-shankar@ouhsc.edu.
Nathan
N
Shankar
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D013293:Enterococcus faecalis / Q000276:immunology*; D016908:Gram-Positive Bacterial Infections / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010538:Peritonitis / Q000276:immunology*; D034741:RNA, Small Interfering / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D037521:Virulence Factors
D001426:Bacterial Proteins; D016207:Cytokines; D018836:Inflammation Mediators; D008565:Membrane Proteins; D016328:NF-kappa B; D034741:RNA, Small Interfering; D037521:Virulence Factors; C116707:enterococcal surface protein, esp
Enterococcus faecalis; Esp; inflammation; pro-inflammatory cytokines; virulence