한빛사 논문
Sohyoung Lee1,4, Yi-An Yang1,4, Shawn K. Milano2, Tri Nguyen1, Changhwan Ahn1, Ji Hyun Sim1, Andrew J. Thompson3, Eric C. Hillpot2, Gyeongshik Yoo1, James C. Paulson3, Jeongmin Song1,5,*
1Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA
2Department of Molecular Medicine, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA
3Department of Molecular Medicine, the Scripps Research Institute, La Jolla, CA 92121, USA
4These authors contributed equally
5Lead Contact
*Corresponding author
Abstract
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.
Keywords : bacterial AB toxins, host adaptations, Salmonella, glycans, glycan expression, structure of protein toxins, cross-reactive protection or immunity, typhoid toxin, typhoid fever, receptor-binding
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