Inhibition of the Classical Pathway of Complement Activation Impairs Bacterial Clearance during Enterococcus faecalis Infection.

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, lectin, and 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 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 defense against E. faecalis.