Severity and properties of cardiac damage caused by Streptococcus pneumoniae are strain dependent

Abstract

Streptococcus pneumoniae is an opportunistic Gram-positive pathogen that can cause invasive disease. Recent studies have shown that S. pneumoniae is able to invade the myocardium and kill cardiomyocytes, with one-in-five adults hospitalized for pneumococcal pneumonia having a pneumonia-associated adverse cardiac event. Furthermore, clinical reports have shown up to a 10-year increased risk of adverse cardiac events in patients formerly hospitalized for pneumococcal bacteremia. In this study, we investigated the ability of nine S. pneumoniae clinical isolates, representing eight unique serotypes, to cause cardiac damage in a mouse model of invasive disease. Following intraperitoneal challenge of C57BL/6 mice, four of these strains (D39, WU2, TIGR4, and 6A-10) caused high-grade bacteremia, while CDC7F:2617–97 and AMQ16 caused mid- and low-grade bacteremia, respectively. Three strains did not cause any discernible disease. Of note, only the strains capable of high-grade bacteremia caused cardiac damage, as inferred by serum levels of cardiac troponin-I. This link between bacteremia and heart damage was further corroborated by Hematoxylin & Eosin and Trichrome staining which showed cardiac cytotoxicity only in D39, WU2, TIGR4, and 6A-10 infected mice. Finally, hearts infected with these strains showed varying histopathological characteristics, such as differential lesion formation and myocytolysis, suggesting that the mechanism of heart damage varied between strains.

Platelets and Their Role in the Pathogenesis of Cardiovascular Events in Patients With Community-Acquired Pneumonia

“…Viasus et al (141) derived a simple rule based on demographic and clinical features that was helpful in identifying patients with CAP at higher risk of acute cardiac events. With regard to bacterial factors of importance, the latter study indicated that those patients with pneumococcal pneumonia appeared to be at greater risk of CVEs and we have highlighted previously in this manuscript additional studies that have noted the importance of pneumococcal bacteremia, and/or infection with pneumococcal serotypes that cause high-grade bacteremia as being most important in respect of this pathogen (30,31). Other authors have suggested that patients with CAP due to Staphylococcus aureus and Klebsiella pneumoniae may also be at increased risk of CVEs (144).…”

“…In their study, Shenoy et al using a murine model of invasive pneumococcal disease, demonstrated that cardiac damage only occurred in the setting of infection with those pneumococcal serotypes that caused high-grade bacteremia (31). Cardiac damage was assessed according to elevated serum cardiac troponin-I levels, as well as cardiac histology that varied according to pneumococcal serotype (31). These findings in the experimental setting confirm those of the clinical study reported by Borsa et al in patients with bacteremic and non-bacteremic pneumococcal pneumonia (30).…”

Pathogenesis and prevention of risk of cardiovascular events in patients with pneumococcal community‐acquired pneumonia

“…Although myocardial damage can also be induced by the systemic administration of recombinant PLY [70], a recent study has demonstrated that in the setting of severe, experimental pneumococcal infection caused by nine different serotypes of the pathogen, induction of cardiac damage is dependent on a high degree of bacteraemia and is also strain specific [71]. Importantly, the nine pneumococcal strains tested varied with respect to their levels of PLY expression, albeit in artificial culture medium in vitro, possibly consistent with serotyperelated, differential involvement of the toxin in the mediation of myocardial damage [71] and/or the ability of the pneumococcus to tightly regulate PLY production according to environmental conditions [72].…”

“…Given that the pneumococcal serotype and extent of bacteraemia appear to be determinants of myocardial invasion, albeit in the setting of experimental disease , measurement of the magnitude of bacterial DNAemia, reported to be a putative marker of disease severity , may also identify those at highest risk of development of acute and even late‐onset CVEs.…”

“…According to the findings of a mouse model of experimental pneumococcal infection, it is only those pneumococcal serotypes capable of high‐grade bacteraemia that cause cardiac damage . In this context, it is also well recognized that the risk of bacteraemia, as well as the risk of death from pneumococcal pneumonia or IPD, is serotype specific .…”