Circulating Pneumolysin Is a Potent Inducer of Cardiac Injury during Pneumococcal Infection

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Cardiac complications frequently accompany invasive disease caused by the pathogen Streptococcus pneumoniae and are associated with significant increases in mortality, however the underlying mechanisms remain elusive. Here, we describe a new mechanism by which pneumococci in the blood stream induce elevation of circulating cardiac troponins; proteins that are markers of cardiac injury and cause inflammatory cell infiltration into the myocardium. We demonstrate that this process is mediated by the circulating pneumococcal toxin pneumolysin (PLY). We also show that antibiotic treatment can exacerbate cardiac injury and dysfunction following pneumococcal infection due to bacterial lysis and the release of PLY, which represents a further mechanistic explanation for the process of cardiac scarring and inflammation. We demonstrate that in addition to its role in inducing death of cardiac cells at high concentrations, PLY at lower (non-lytic) concentrations trigger a range of cellular events starting with cellular membrane pore-formation, substantial calcium overload which then mediates mechanical and electrical disturbance to the function of cardiac cells. Our work proposes that novel translational strategies to detect and neutralize circulating PLY during pneumococcal disease could be utilized to assess disease severity and should be targeted for prevention/treatment purposes.

Vyšlo v časopise: Circulating Pneumolysin Is a Potent Inducer of Cardiac Injury during Pneumococcal Infection. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004836
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004836

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