North Carolina State University, College of Veterinary Medicine, 4700 Hillsborough Street, Raleigh, NC 27606, USA.
Vet Pathol. 2013 May;50(3):457-67. doi: 10.1177/0300985811424731. Epub 2011 Oct 12.
Group C streptococci are highly contagious pyogenic bacteria responsible for respiratory tract, lymph node, urogenital tract, and wound infections. Wild-type strains of Streptococcus equi ssp equi (S. equi) and Streptococcus equi ssp zooepidemicus (S. zoo) as well as a commercially available modified live vaccine strain of S. equi were evaluated for virulence in zebrafish. Survival times, histologic lesions, and relative gene expression were compared among groups. Based on the intramuscular route of infection, significantly shorter survival times were observed in fish infected with wild-type strain when compared to modified live vaccine and S. zoo strains. Histologically, S. zoo-infected fish demonstrated a marked increase in inflammatory infiltrates (predominantly macrophages) at the site of infection, as well as increased cellularity in the spleen and renal interstitium. In contrast, minimal cellular immune response was observed in S. equi-injected fish with local tissue necrosis and edema predominating. Based on whole comparative genomic hybridization, increased transcription of positive acute-phase proteins, coagulation factors, and antimicrobial peptides were observed in S. equi-injected fish relative to S. zoo-injected fish, while mediators of cellular inflammation, including CXC chemokines and granulin, were upregulated in S. zoo-injected fish relative to S. equi-injected fish. In a screen of 11 clinical isolates, S. equi strains with a single nucleotide deletion in the upstream region of szp, a known virulence factor of streptococci, were found to be significantly attenuated in zebrafish. These collective findings underscore the value of the zebrafish as a model of streptococcal pathogenesis.
C 群链球菌是一种高度传染性化脓性细菌，可引起呼吸道、淋巴结、泌尿生殖道和创伤感染。对马链球菌兽疫亚种（S. equi）和马链球菌兽疫亚种（S. zooepidemicus）的野生型菌株以及一种市售的马链球菌改良活疫苗株进行了毒力评估。比较了各组的存活时间、组织学病变和相对基因表达。基于肌肉内感染途径，与改良活疫苗株和 S. zoo 株相比，野生型菌株感染的鱼存活时间明显缩短。组织学上，S. zoo 感染的鱼在感染部位炎症浸润（主要为巨噬细胞）明显增加，脾脏和肾间质细胞增多。相比之下，在 S. equi 注射的鱼中观察到局部组织坏死和水肿为主的最小细胞免疫反应。基于全比较基因组杂交，与 S. zoo 注射的鱼相比，S. equi 注射的鱼中急性期蛋白、凝血因子和抗菌肽的转录增加，而 S. zoo 注射的鱼中细胞炎症的介质，包括 CXC 趋化因子和颗粒素，上调。在对 11 株临床分离株的筛选中，发现 szp 上游区域单个核苷酸缺失的 S. equi 菌株在斑马鱼中明显减弱。这些研究结果强调了斑马鱼作为链球菌发病机制模型的价值。
