Severity and properties of cardiac damage caused by <i>Streptococcus pneumoniae</i> are strain dependent

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.肺炎链球菌（Streptococcus pneumoniae）是一类机会致病性革兰氏阳性病原菌，可引发侵袭性感染疾病。近期研究证实，肺炎链球菌能够侵袭心肌组织并杀伤心肌细胞；每5名因肺炎链球菌肺炎住院的成人中，即有1例会发生肺炎相关不良心脏事件。此外，临床报告显示，既往因肺炎链球菌菌血症住院的患者，其不良心脏事件的发病风险最高可升高长达10年。本研究中，我们针对代表8种独特血清型的9株肺炎链球菌临床分离株，在侵袭性疾病小鼠模型中探究其诱发心脏损伤的能力。对C57BL/6小鼠实施腹腔攻毒后，其中4株（D39、WU2、TIGR4及6A-10）可引发重度菌血症，而CDC7F:2617–97与AMQ16分别引发中度与轻度菌血症，剩余3株未引发任何可观测到的病症。值得关注的是，仅那些能够引发重度菌血症的菌株才会造成心脏损伤，该结论可通过血清中心肌肌钙蛋白-I（cardiac troponin-I）的水平予以推断。菌血症与心脏损伤之间的这一关联，进一步通过苏木精-伊红（Hematoxylin & Eosin）染色与三色（Trichrome）染色得到验证：仅在感染D39、WU2、TIGR4及6A-10的小鼠心脏中，可观察到心脏细胞毒性现象。最后，感染上述菌株的小鼠心脏呈现出多样化的组织病理学特征，如不同类型的病灶形成与心肌细胞溶解，这提示不同菌株引发心脏损伤的机制存在菌株间差异。