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Background Enterococcus faecalis is considered to be the most important species of enterococci responsible for blood stream infections in critically ill patients. In blood, the complement system is activated via the classical pathway (CP), the lectin pathway (LP), or the alternative pathway (AP), and it plays a critical role in opsonophagocytosis of bacteria including E faecalis. Methods In a mouse model of enterococcus peritonitis, BALB-C mice were challenged with a high dose of E faecalis 12 hours after intraperitoneal administration of anti-Factor H (FH) antibodies or isotype control. Four hours later, control mice developed higher bacterial burden in blood and organs compared with mice treated with anti-FH antibodies. Results We demonstrate that complement recognition molecules C1q, CL-11, and murine ficolin-A bind the enterococcus and drive the CP and the LP in human and mouse. We further describe that E faecalis evades the AP by recruitment of FH on its surface. Our results show a strong C3b deposition on E faecalis via both the CP and the LP but not through the AP. Conclusions These findings indicate that E faecalis avoids the complement phagocytosis by the AP via sequestering complement FH from the host blood.

Enterococcus faecalis infections are considered a major public health concern worldwide. The complement system has a crucial role in the protection against different microbial pathogens including E. faecalis. Complement can be activated through three different pathways including; the classical, the lectin, and the alternative pathways. There is limited information on the role of the classical pathway (CP) in protection against infections caused by E. faecalis. In the present study, we generated Fab fragments that successfully block the CP in mouse via inhibition of a key enzyme C1s-A. Our results showed that anti C1s-A Fab fragments block CP mediated C3b and C4b deposition in vitro. We further showed that administration of anti C1s-A Fab fragments significantly impairs the CP functional activity in vitro and in vivo. Moreover, treatment of mice infected with E. faecalis using anti C1s-A Fab fragments significantly impairs bacterial clearance as determined from the viable bacterial counts recovered from blood, kidneys, spleens, livers, and lungs of infected mice. Overall, this study highlights the essential role of the CP in host defence against E. faecalis.