Cardiac Microlesions Form During Severe Bacteremic Enterococcus faecalis Infection

Abstract

AbstractEnterococcus faecalis is a significant cause of hospital-acquired bacteremia. Herein, the discovery is reported that cardiac microlesions form during severe bacteremic E. faecalis infection in mice. The cardiac microlesions were identical in appearance to those formed by Streptococcus pneumoniae during invasive pneumococcal disease (IPD). However, E. faecalis does not encode the virulence determinants implicated in pneumococcal microlesion formation. Rather, disulfide bond forming protein DsbA was found to be required for E. faecalis virulence in a C. elegans model and was necessary for efficient cardiac microlesion formation. Furthermore, E. faecalis promoted cardiomyocyte apoptotic and necroptotic cell death at sites of microlesion formation. Additionally, loss of DsbA caused an increase in pro-inflammatory cytokines unlike the wild-type strain, which suppressed the immune response. In conclusion, we establish that E. faecalis is capable of forming cardiac microlesions and identify features of both the bacterium and the host response that are mechanistically involved.SUMMARYThis work presents the observation of cardiac microlesion formation during severe blood stream infection with Enterococcus faecalis in mice. Moreover, we identify the contribution of a novel enterococcal virulence determinant in modulating microlesion formation and the host immune response.