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

Journal Article · · Cell Host & Microbe
 [1];  [1];  [2];  [1];  [1];  [1];  [3];  [2];  [1];  [3];  [1]
  1. Cornell Univ. College of Veterinary Medicine, Ithaca, NY (United States). Dept. of Microbiology and Immunology
  2. Cornell Univ. College of Veterinary Medicine, Ithaca, NY (United States). Dept. of Molecular Medicine
  3. The Scripps Research Inst., La Jolla, CA (United States). Dept. of Molecular Medicine
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.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
USDOE; USDOE Office of Science (SC)
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1834871
Alternate ID(s):
OSTI ID: 1839763
OSTI ID: 1632976
Journal Information:
Cell Host & Microbe, Journal Name: Cell Host & Microbe Journal Issue: 6 Vol. 27; ISSN 1931-3128
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

References (37)

Serodiagnostic evaluation of recombinant CdtB of S. Typhi as a potential candidate for acute typhoid journal June 2018
[20] Processing of X-ray diffraction data collected in oscillation mode book January 1997
Host Adaptation of a Bacterial Toxin from the Human Pathogen Salmonella Typhi journal December 2014
Delivery of a Salmonella Typhi Exotoxin from a Host Intracellular Compartment journal January 2008
A Mouse Model for the Human Pathogen Salmonella Typhi journal October 2010
Receptor-Mediated Sorting of Typhoid Toxin during Its Export from Salmonella Typhi-Infected Cells journal November 2016
Recent H3N2 Viruses Have Evolved Specificity for Extended, Branched Human-type Receptors, Conferring Potential for Increased Avidity journal January 2017
An evaluation of purified Salmonella Typhi protein antigens for the serological diagnosis of acute typhoid fever journal August 2017
A novel pathway for exotoxin delivery by an intracellular pathogen journal February 2008
Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18 journal October 2001
Incorporation of a non-human glycan mediates human susceptibility to a bacterial toxin journal December 2008
Structure and function of the Salmonella Typhi chimaeric A2B5 typhoid toxin journal July 2013
Enzymatic assembly of DNA molecules up to several hundred kilobases journal April 2009
Evolution of host adaptation in the Salmonella typhoid toxin journal October 2017
In vivo tropism of Salmonella Typhi toxin to cells expressing a multiantennal glycan receptor journal December 2017
Immune profiling with a Salmonella Typhi antigen microarray identifies new diagnostic biomarkers of human typhoid journal January 2013
Salmonella typhi encodes a functional cytolethal distending toxin that is delivered into host cells by a bacterial-internalization pathway journal March 2004
Inactivation of CMP-N-acetylneuraminic acid hydroxylase occurred prior to brain expansion during human evolution journal August 2002
A Retrospective Study of Laboratory-Based Enteric Fever Surveillance, Pakistan, 2012–2014 journal July 2018
FastME 2.0: A Comprehensive, Accurate, and Fast Distance-Based Phylogeny Inference Program: Table 1. journal June 2015
A Hidden Markov Model approach to variation among sites in rate of evolution journal January 1996
PHENIX: a comprehensive Python-based system for macromolecular structure solution journal January 2010
Features and development of Coot journal March 2010
Typhoidal Salmonella : Distinctive virulence factors and pathogenesis journal August 2018
Spectrum of neuropsychiatric complications in 791 cases of typhoid fever journal April 1997
Immunoproteomic Analysis of Antibody in Lymphocyte Supernatant in Patients with Typhoid Fever in Bangladesh journal December 2013
How To Become a Top Model: Impact of Animal Experimentation on Human Salmonella Disease Research journal February 2011
Emergence of an Extensively Drug-Resistant Salmonella enterica Serovar Typhi Clone Harboring a Promiscuous Plasmid Encoding Resistance to Fluoroquinolones and Third-Generation Cephalosporins journal February 2018
Salmonella: A Model for Bacterial Pathogenesis journal February 2001
Genome sequencing reveals diversification of virulence factor content and possible host adaptation in distinct subpopulations of Salmonella enterica journal August 2011
Rapid Emergence of Multidrug Resistant, H58-Lineage Salmonella Typhi in Blantyre, Malawi journal April 2015
Neurologic Manifestations Associated with an Outbreak of Typhoid Fever, Malawi - Mozambique, 2009: An Epidemiologic Investigation journal December 2012
The role of 9-O-acetylated glycan receptor moieties in the typhoid toxin binding and intoxication journal February 2020
Outbreak-associated Salmonella enterica Serotypes and Food Commodities, United States, 1998–2008 journal August 2013
Same species, different diseases: how and why typhoidal and non-typhoidal Salmonella enterica serovars differ journal August 2014
Why Is Eradicating Typhoid Fever So Challenging: Implications for Vaccine and Therapeutic Design journal July 2018
Systematic review of the global epidemiology, clinical and laboratory profile of enteric fever journal November 2015

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