Sahin Orhan, Terhorst Samantha A, Burrough Eric R, Shen Zhangqi, Wu Zuowei, Dai Lei, Tang Yizhi, Plummer Paul J, Ji Ju, Yaeger Michael J, Zhang Qijing
Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, Iowa, USA.
Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, Ames, Iowa, USA.
Infect Immun. 2017 May 23;85(6). doi: 10.1128/IAI.00001-17. Print 2017 Jun.
is a zoonotic pathogen, and a hypervirulent clone, named clone SA, has recently emerged as the predominant cause of ovine abortion in the United States. To induce abortion, orally ingested must translocate across the intestinal epithelium, spread systemically in the circulation, and reach the fetoplacental tissue. Bacterial factors involved in these steps are not well understood. is known to produce capsular polysaccharide (CPS), but the specific role that CPS plays in systemic infection and particularly abortion in animals remains to be determined. In this study, we evaluated the role of CPS in bacteremia using a mouse model and in abortion using a pregnant guinea pig model following oral challenge. Compared with NCTC 11168 and 81-176, a clone SA isolate (IA3902) resulted in significantly higher bacterial counts and a significantly longer duration of bacteremia in mice. The loss of capsule production via gene-specific mutagenesis in IA3902 led to the complete abolishment of bacteremia in mice and abortion in pregnant guinea pigs, while complementation of capsule expression almost fully restored these phenotypes. The capsule mutant strain was also impaired for survival in guinea pig sera and sheep blood. Sequence-based analyses revealed that clone SA possesses a unique CPS locus with a mosaic structure, which has been stably maintained in all clone SA isolates derived from various hosts and times. These findings establish CPS as a key virulence factor for the induction of systemic infection and abortion in pregnant animals and provide a viable candidate for the development of vaccines against hypervirulent .
是一种人畜共患病原体,一种名为克隆SA的高毒力克隆最近已成为美国绵羊流产的主要原因。为了诱导流产,口服摄入的必须穿过肠上皮细胞,在循环系统中全身扩散,并到达胎儿胎盘组织。参与这些步骤的细菌因素尚不清楚。已知会产生荚膜多糖(CPS),但CPS在全身感染尤其是动物流产中所起的具体作用仍有待确定。在本研究中,我们使用小鼠模型评估了CPS在菌血症中的作用,并在口服攻击后使用怀孕豚鼠模型评估了其在流产中的作用。与NCTC 11168和81-176相比,克隆SA分离株(IA3902)在小鼠中导致显著更高的细菌计数和更长的菌血症持续时间。通过IA3902中的基因特异性诱变导致荚膜产生丧失,导致小鼠菌血症完全消除以及怀孕豚鼠流产,而荚膜表达的互补几乎完全恢复了这些表型。荚膜突变株在豚鼠血清和绵羊血液中的存活能力也受损。基于序列分析表明,克隆SA拥有一个具有镶嵌结构的独特CPS基因座,该结构在来自不同宿主和时间的所有克隆SA分离株中都得到了稳定维持。这些发现确定CPS是诱导怀孕动物全身感染和流产的关键毒力因子,并为开发针对高毒力的疫苗提供了一个可行的候选物。