Cardiac Microlesions Form During Severe Bacteremic Enterococcus faecalis Infection
Cardiac Microlesions Form During Severe Bacteremic Enterococcus faecalis Infection
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DOI：
10.1093/infdis/jiaa371
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发表时间：
2021-02-01
影响因子：
6.4
通讯作者：
Garsin, Danielle A.
中科院分区：
文献类型：
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作者：
Brown, Armand O.;Singh, Kavindra, V;Garsin, Danielle A.
粪肠球菌是医院获得性菌血症的重要原因。本研究发现，小鼠在严重的粪肠杆菌感染期间可形成心脏微病变。心脏微病变在外观上与侵袭性肺炎球菌病期间由肺炎链球菌形成的病变相同。然而，粪肠球菌不编码与肺炎球菌微病变形成有关的毒力决定因素。相反，在秀丽隐杆线虫模型中发现，二硫键形成蛋白A （DsbA）是E. faecalis毒力所必需的，也是有效的心脏微病变形成所必需的。此外，粪肠杆菌促进微病变形成部位心肌细胞凋亡和坏死细胞死亡。此外，DsbA的缺失导致促炎细胞因子的增加，这与野生型菌株不同，后者会抑制免疫反应。总之，我们确定了粪肠杆菌能够形成心脏微病变，并确定了细菌和宿主反应的机制参与特征。
Enterococcus faecalis is a significant cause of hospital-acquired bacteremia. Herein, the discovery is reported that cardiac microlesions form during severe bacteremic E. faecalis infection in mice. The cardiac microlesions were identical in appearance to those formed by Streptococcus pneumoniae during invasive pneumococcal disease. However, E. faecalis does not encode the virulence determinants implicated in pneumococcal microlesion formation. Rather, disulfide bond forming protein A (DsbA) was found to be required for E. faecalis virulence in a Caenorhabditis elegans model and was necessary for efficient cardiac microlesion formation. Furthermore, E. faecalis promoted cardiomyocyte apoptotic and necroptotic cell death at sites of microlesion formation. Additionally, loss of DsbA caused an increase in proinflammatory cytokines, unlike the wild-type strain, which suppressed the immune response. In conclusion, we establish that E. faecalis is capable of forming cardiac microlesions and identify features of both the bacterium and the host response that are mechanistically involved.