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Cardiotoxicity during invasive pneumococcal disease

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Title: Cardiotoxicity during invasive pneumococcal disease
Authors: Brown, AO
Millett, ERC
Quint, JK
Orihuela, CJ
Item Type: Journal Article
Abstract: Copyright © 2015 by the American Thoracic Society.Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and sepsis, with adult hospitalization linked to approximately 19% incidence of an adverse cardiac event (e.g., heart failure, arrhythmia, infarction). Herein, we review the specific host-pathogen interactions that contribute to cardiac dysfunction during invasive pneumococcal disease: (1) cell wall-mediated inhibition of cardiomyocyte contractility; (2) the new observation that S. pneumoniae is capable of translocation into the myocardium and within the heart, forming discrete, nonpurulent, microscopic lesions that are filled with pneumococci; and (3) the bacterial virulence determinants, pneumolysin and hydrogen peroxide, that are most likely responsible for cardiomyocyte cell death. Pneumococcal invasion of heart tissue is dependent on the bacterial adhesin choline-binding protein A that binds to laminin receptor on vascular endothelial cells and binding of phosphorylcholine residues on pneumococcal cell wall to platelet-activating factor receptor. These are the same interactions responsible for pneumococcal translocation across the blood-brain barrier during the development of meningitis. We discuss these interactions and how their neutralization, either with antibody or therapeutic agents that modulate platelet-activating factor receptor expression, may confer protection against cardiac damage and meningitis. Considerable collagen deposition was observed in hearts of mice that had recovered from invasive pneumococcal disease. We discuss the possibility that cardiac scar formation after severe pneumococcal infection may explain why individuals who are hospitalized for pneumonia are at greater risk for sudden death up to 1 year after infection.
Issue Date: 1-Apr-2015
Date of Acceptance: 19-Jan-2015
URI: http://hdl.handle.net/10044/1/27147
DOI: https://dx.doi.org/10.1164/rccm.201411-1951PP
ISSN: 1073-449X
Start Page: 739
End Page: 745
Journal / Book Title: American Journal of Respiratory and Critical Care Medicine
Volume: 191
Issue: 7
Copyright Statement: © 2015 by the American Thoracic Society Read More: http://www.atsjournals.org/doi/10.1164/rccm.201411-1951PP#.VjI38ytRRCA
Publication Status: Published
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



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