Salmonella Typhoid Toxin PltB Subunit and Its Non-typhoidal Salmonella Ortholog Confer Differential Host Adaptation and Virulence

Lee Sohyoung; Yang Yi-An; Milano Shawn K.; Nguyen Tri; Ahn Changhwan; Sim Ji Hyun; Thompson Andrew J.; Hillpot Eric C.; Yoo Gyeongshik; Paulson James C.; Song Jeongmin

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Salmonella Typhoid Toxin PltB Subunit and Its Non-typhoidal Salmonella Ortholog Confer Differential Host Adaptation and Virulence

机译：沙门氏菌毒素毒素PLTB亚单位及其非胸腺沙门氏菌矫正宿主适应和毒力

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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.

机译：伤寒和非伤寒沙门氏菌（NTS）分别引起人类伤寒和胃肠炎。伤寒沙门氏菌毒素有助于伤寒疾病的进展和慢性感染，但对其NTS同源体的作用知之甚少。我们发现伤寒毒素和它的NTS同源物引起不同的临床表现。每种毒素的PltB亚单位都表现出不同的聚糖结合偏好，与每种细菌在主要感染或中毒部位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亚单位的共晶结构，我们表明它们诱导显著不同的聚糖结合偏好和毒力结果。此外，用NTS S.Javiana或其毒素免疫可提供交叉反应保护，以抵抗致命剂量伤寒毒素的挑战。累积起来，这些结果为研究沙门氏菌AB毒素宿主适应的演变、其细胞和组织取向以及改进伤寒疫苗和疗法的设计提供了见解。

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《Cell Host & Microbe》 |2020年第6期|共19页
作者
Lee Sohyoung; Yang Yi-An; Milano Shawn K.; Nguyen Tri; Ahn Changhwan; Sim Ji Hyun; Thompson Andrew J.; Hillpot Eric C.; Yoo Gyeongshik; Paulson James C.; Song Jeongmin;
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作者单位

Cornell Univ Dept Microbiol &

Immunol Coll Vet Med Ithaca NY 14853 USA;

Cornell Univ Dept Microbiol &

Immunol Coll Vet Med Ithaca NY 14853 USA;

Cornell Univ Dept Mol Med Coll Vet Med Ithaca NY 14853 USA;

Cornell Univ Dept Microbiol &

Immunol Coll Vet Med Ithaca NY 14853 USA;

Cornell Univ Dept Microbiol &

Immunol Coll Vet Med Ithaca NY 14853 USA;

Cornell Univ Dept Microbiol &

Immunol Coll Vet Med Ithaca NY 14853 USA;

Scripps Res Inst Dept Mol Med La Jolla CA 92121 USA;

Cornell Univ Dept Mol Med Coll Vet Med Ithaca NY 14853 USA;

Cornell Univ Dept Microbiol &

Immunol Coll Vet Med Ithaca NY 14853 USA;

Scripps Res Inst Dept Mol Med La Jolla CA 92121 USA;

Cornell Univ Dept Microbiol &

Immunol Coll Vet Med Ithaca NY 14853 USA;

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正文语种 eng
中图分类普通生物学;
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1. Antibiotic resistance and molecular characterization of diarrheagenic Escherichia coli and non-typhoidal Salmonella strains isolated from infections in Southwest China [J] . Shun-Xian Zhang, Jun-Hu Chen, Shang Xia, 贫困所致传染病（英文） . 2018,第003期
2. Antibiotic resistance and molecular characterization of diarrheagenic Escherichia coli and non-typhoidal Salmonella strains isolated from infections in Southwest China [J] . Shun-Xian Zhang, Yong-Ming Zhou, Li-Guang Tian, 贫困所致传染病（英文） . 2018,第001期
3. Immune dynamics following infection of avian macrophages and epithelial cells with typhoidal and non-typhoidal Salmonella enterica serovars; bacterial invasion and persistence, nitric oxide and oxygen production, differential host gene expression, NF- kappa B signalling and cell cytotoxicity. [J] . Setta A., Barrow P. A., Kaiser P., Veterinary Immunology and Immunopathology . 2012,第3a4期

机译：伤寒和非伤寒性沙门氏菌肠病毒感染禽巨噬细胞和上皮细胞后的免疫动力学;细菌入侵和持久性，一氧化氮和氧气产生，宿主基因差异表达，NF-κB信号传导和细胞毒性。
4. The Possible Influence of Non-synonymous Point Mutations within the FimA Adhesin of Non-typhoidal Salmonella (NTS) Isolates in the Process of Host Adaptation [J] . Sahar Alshalchi, Shivdeep S. Hayer, Ran An, Frontiers in Microbiology . 2017,第6期

机译：非伤寒沙门氏菌（NTS）分离株的FimA粘附素内非同义点突变在宿主适应过程中的可能影响。
5. Evolution of host adaptation in the Salmonella typhoid toxin [J] . Xiang Gao, Lingquan Deng, Gabrielle Stack, Nature Microbiology . 2017,第12期

机译：沙门氏菌毒素毒素中宿主适应的演变
6. Immunogenicity evaluation of recombinant fim-c salmonella typhi protein as typhoid vaccine candidate on wistar rat [C] . M Nurjayadi, IR Kartika, F Kumiadewi Annual Applied Science and Engineering Conference . 2019

机译：重组FIM-C沙门氏菌Typhi蛋白作为Wistar大鼠伤寒疫苗候选的免疫原性评价
7. Shift in the Relative Importance of Different Serovars Causing Invasive Non-Typhoidal Salmonella (iNTS) Disease in Mali and the Potential Role for NTS Vaccines to Diminish Disease Burden. [D] . Bornstein, Kristin. 2017

机译：马里侵袭性非伤寒沙门氏菌（iNTS）病引起的不同血清型相对重要性的转移以及NTS疫苗减轻疾病负担的潜在作用。
8. The Possible Influence of Non-synonymous Point Mutations within the FimA Adhesin of Non-typhoidal Salmonella (NTS) Isolates in the Process of Host Adaptation [O] . Sahar Alshalchi, Shivdeep S. Hayer, Ran An, -1

机译：非伤寒沙门氏菌（NTS）分离株的FimA粘附素内非同义点突变在宿主适应过程中的可能影响。
9. The Possible Influence of Non-synonymous Point Mutations within the FimA Adhesin of Non-typhoidal Salmonella (NTS) Isolates in the Process of Host Adaptation [O] . Sahar Alshalchi, Shivdeep S. Hayer, Ran An, 2017

机译：非宿主沙门氏菌（NTs）分离株Fima粘附素在宿主适应过程中非同义点突变的可能影响
10. Genetically Conferred Defect in Anti-Salmonella Antibody Formation Renders CBA/N Mice Innately Susceptible to Salmonella Typhimurium Infection [R] . O'Brien, A. D., Scher, I., Metcalf, E. S. 1980

机译：抗沙门氏菌抗体形成的基因传递缺陷使CBa / N小鼠易感染鼠伤寒沙门氏菌感染

Salmonella Typhoid Toxin PltB Subunit and Its Non-typhoidal Salmonella Ortholog Confer Differential Host Adaptation and Virulence

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