Salmonella Typhoid Toxin PltB Subunit and Its Non-typhoidal Salmonella Ortholog Confer Differential Host Adaptation and Virulence
Salmonella Typhoid Toxin PltB Subunit and Its Non-typhoidal Salmonella Ortholog Confer Differential Host Adaptation and Virulence
复制标题
DOI：
10.1016/j.chom.2020.04.005
复制
发表时间：
2020-06-10
影响因子：
30.3
通讯作者：
Song, Jeongmin
中科院分区：
文献类型：
--
作者：
Lee, Sohyoung;Yang, Yi-An;Song, Jeongmin
伤寒沙门氏菌属和非伤寒沙门氏菌属分别在人类中引起伤寒和胃肠炎。沙门氏菌伤寒毒素有助于伤寒疾病的进展和慢性感染，但很少有人知道它的NTS直系同源物的作用。我们发现伤寒毒素和它的NTS直系同源物诱导不同的临床表现。每种毒素的PltB亚基表现出不同的聚糖结合偏好，其与在原发感染或中毒位点处由每种细菌靶向的宿主细胞的聚糖表达谱相关。通过与特定聚糖受体部分结合的PltB亚基的共晶体结构，我们表明它们诱导明显不同的聚糖结合偏好和毒力结果。此外，用NTS S. Javiana或其毒素提供交叉反应保护，对抗致死剂量伤寒毒素攻击。累积起来，这些结果提供了深入了解沙门氏菌AB毒素，它们的细胞和组织向性，以及改进伤寒疫苗和治疗方法的设计的宿主适应的演变。
Typhoidal and non-typhoidal Salmonelleae (NTS) cause typhoid fever and gastroenteritis, respectively, in humans. Salmonella typhoid toxin contributes to typhoid disease progression and chronic infection, but little is known about the role of its NTS ortholog. We found that typhoid toxin and its NTS ortholog induce different clinical presentations. The PltB subunit of each toxin exhibits different glycan-binding preferences that correlate with glycan expression profiles of host cells targeted by each bacterium at the primary infection or intoxication sites. Through co-crystal structures of PltB subunits bound to specific glycan receptor moieties, we show that they induce markedly different glycan-binding preferences and virulence outcomes. Furthermore, immunization with the NTS S. Javiana or its toxin offers cross-reactive protection against lethal-dose typhoid toxin challenge. Cumulatively, these results offer insights into the evolution of host adaptations in Salmonella AB toxins, their cell and tissue tropisms, and the design for improved typhoid vaccines and therapeutics.