Hospitalization for community-acquired pneumonia carries a documented risk for adverse cardiac events. These occur during infection and contribute to elevated mortality rates in convalescent individuals up to a year after. A new paper describes a previously unrecognized pathogenic mechanism by which Streptococcus pneumoniae, the leading cause of community-acquired pneumonia, causes direct cardiotoxicity and forms microscopic bacteria-filled lesions within the heart.
Cardiac microlesions were detected in experimentally infected mice and rhesus macaques, as well as in heart sections from humans who succumbed to invasive pneumococcal disease. Cardiac microlesion formation required interaction of the bacterial adhesin CbpA with host laminin receptor and bacterial cell wall with platelet-activating factor receptor and also involved the pore-forming toxin pneumolysin. When infected mice were rescued with antibiotics, collagen deposition occurs at former lesion sites. Thus, microlesions and the scarring that occurs thereafter may explain why adverse cardiac events occur during and following pneumococcal disease.
Streptococcus pneumoniae Translocates into the Myocardium and Forms Unique Microlesions That Disrupt Cardiac Function. (2014) PLoS Pathog 10(9): e1004383. doi:10.1371/journal.ppat.1004383
Hospitalization of the elderly for invasive pneumococcal disease is frequently accompanied by the occurrence of an adverse cardiac event; these are primarily new or worsened heart failure and cardiac arrhythmia. Herein, we describe previously unrecognized microscopic lesions (microlesions) formed within the myocardium of mice, rhesus macaques, and humans during bacteremic Streptococcus pneumoniae infection. In mice, invasive pneumococcal disease (IPD) severity correlated with levels of serum troponin, a marker for cardiac damage, the development of aberrant cardiac electrophysiology, and the number and size of cardiac microlesions. Microlesions were prominent in the ventricles, vacuolar in appearance with extracellular pneumococci, and remarkable due to the absence of infiltrating immune cells. The pore-forming toxin pneumolysin was required for microlesion formation but Interleukin-1b was not detected at the microlesion site ruling out pneumolysin-mediated pyroptosis as a cause of cell death. Antibiotic treatment resulted in maturing of the lesions over one week with robust immune cell infiltration and collagen deposition suggestive of long-term cardiac scarring. Bacterial translocation into the heart tissue required the pneumococcal adhesin CbpA and the host ligands Laminin receptor (LR) and Platelet-activating factor receptor. Immunization of mice with a fusion construct of CbpA or the LR binding domain of CbpA with the pneumolysin toxoid L460D protected against microlesion formation. We conclude that microlesion formation may contribute to the acute and long-term adverse cardiac events seen in humans with IPD.