Brown AO(1), Singh KV(2), Cruz MR(1), Kaval KG(1), Francisco LE(3), Murray BE(1)(2), Garsin DA(1). Author information:
(1)Department of Microbiology and Molecular Genetics, University of Texas Health
Science Center at Houston, Houston, Texas, USA.
(2)Division of Infectious Diseases, Department of Internal Medicine, University
of Texas Health Science Center at Houston, Houston, Texas, USA.
(3)Department of Biochemistry and Structural Biology, University of Texas Health
Science Center at San Antonio, San Antonio, Texas, USA.
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.
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