Campylobacter jejuni 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 Campylobacter 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. C. jejuni 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 C. jejuni 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 C. jejuni.

译文

空肠弯曲菌是一种人畜共患的病原体,最近在美国出现了一种名为克隆SA的高毒力克隆,是绵羊流产的主要原因。为了引起流产,口服摄入的弯曲杆菌必须在整个肠上皮中转位,在循环中全身扩散,并到达胎盘组织。参与这些步骤的细菌因素尚不清楚。空肠杆菌可产生荚膜多糖 (CPS),但CPS在全身感染尤其是动物流产中的具体作用仍有待确定。在这项研究中,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的豚鼠模型评估了CPS在流产中的作用。与空肠杆菌NCTC 11168和81-176相比,克隆SA分离物 (IA3902) 在小鼠中导致明显更高的细菌计数和明显更长的菌血症持续时间。在IA3902中,通过基因特异性诱变导致胶囊产生的损失导致小鼠菌血症的完全消除和怀孕豚鼠的流产,而胶囊表达的互补几乎完全恢复了这些表型。胶囊突变株在豚鼠血清和绵羊血液中的存活也受到损害。基于序列的分析表明,克隆SA具有独特的CPS基因座,具有镶嵌结构,在来自各种宿主和时间的所有克隆SA分离株中均保持稳定。这些发现将CPS确定为诱导妊娠动物全身感染和流产的关键毒力因子,并为开发针对高毒性空肠杆菌的疫苗提供了可行的候选者。

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