Department of Microbiology and Molecular Genetics, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Division of Infectious Diseases, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
J Infect Dis. 2021 Feb 13;223(3):508-516. doi: 10.1093/infdis/jiaa371.
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.
粪肠球菌是医院获得性菌血症的重要病因。本研究发现,严重的肠球菌菌血症感染小鼠会形成心脏微损伤。这些心脏微损伤与肺炎链球菌引起的侵袭性肺炎球菌病所形成的损伤在外观上完全相同。然而,肠球菌并不编码与肺炎链球菌微损伤形成相关的毒力决定因素。相反,发现二硫键形成蛋白 A(DsbA)对于线虫模型中的肠球菌毒力是必需的,并且对于有效的心脏微损伤形成也是必需的。此外,肠球菌在微损伤形成部位促进心肌细胞凋亡和坏死性细胞死亡。此外,与野生型菌株不同,DsbA 的缺失会导致促炎细胞因子的增加,而野生型菌株则抑制免疫反应。总之,我们证实了肠球菌能够形成心脏微损伤,并确定了细菌和宿主反应的特征,这些特征在机制上涉及其中。