Cardiac Microlesions Form During Severe Bacteremic Enterococcus faecalis Infection. (29th June 2020)

• Record Type: Journal Article
• Authors: Brown, Armand O; Singh, Kavindra V; Cruz, Melissa R; Kaval, Karan Gautam; Francisco, Liezl E; Murray, Barbara E; Garsin, Danielle A
• Is Part Of: Journal of infectious diseases. Volume 223:Number 3(2021)
• Page Start: 508
• Page End: 516
• Publication Date: 2020-06-29
• Subjects: Enterococcus faecalis -- cardiac -- microlesions -- sepsis -- bacteremia -- infection -- virulence -- thioredoxin -- disulfide bond -- necroptosis; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiaa371
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Enterococcus 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. However, E. faecalis does not encode the virulence determinants implicated in pneumococcal microlesion formation. Rather, disulfide bond forming protein A (DsbA) was found to be required for E. faecalis virulence in a Caenorhabditis 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 proinflammatory 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. Abstract : This work presents the observation of cardiac microlesion formation during severe bloodstream 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.