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Conferring Virulence: Structure and Function of the chimeric A(2)B(5) Typhoid Toxin
Salmonella Typhi differs from most other salmonellae in that it causes a life-threatening systemic infection known as typhoid fever(1). The molecular bases for its unique clinical presentation are unknown(2). Here we found that in an animal model, the systemic administration of typhoid toxin, a uniq...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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2013
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144355/ https://www.ncbi.nlm.nih.gov/pubmed/23842500 http://dx.doi.org/10.1038/nature12377 |
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author | Song, Jeongmin Gao, Xiang Galán, Jorge E. |
author_facet | Song, Jeongmin Gao, Xiang Galán, Jorge E. |
author_sort | Song, Jeongmin |
collection | PubMed |
description | Salmonella Typhi differs from most other salmonellae in that it causes a life-threatening systemic infection known as typhoid fever(1). The molecular bases for its unique clinical presentation are unknown(2). Here we found that in an animal model, the systemic administration of typhoid toxin, a unique virulence factor of S. Typhi, reproduces many of the acute symptoms of typhoid fever. We identified specific carbohydrate moieties on specific surface glycoproteins that serve as receptors for typhoid toxin, which explains its broad cell target specificity. We present the atomic structure of typhoid toxin, which shows an unprecedented A(2)B(5) organization with two covalently-linked A subunits non-covalently-associated to a pentameric B subunit. The structure provides insight into the toxin’s receptor-binding specificity and delivery mechanisms and reveals how the activities of two powerful toxins have been coopted into a single, unique toxin that can induce many of the symptoms characteristic of typhoid fever. These findings may lead to the development of potentially life-saving therapeutics against typhoid fever. |
format | Online Article Text |
id | pubmed-4144355 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
record_format | MEDLINE/PubMed |
spelling | pubmed-41443552014-08-26 Conferring Virulence: Structure and Function of the chimeric A(2)B(5) Typhoid Toxin Song, Jeongmin Gao, Xiang Galán, Jorge E. Nature Article Salmonella Typhi differs from most other salmonellae in that it causes a life-threatening systemic infection known as typhoid fever(1). The molecular bases for its unique clinical presentation are unknown(2). Here we found that in an animal model, the systemic administration of typhoid toxin, a unique virulence factor of S. Typhi, reproduces many of the acute symptoms of typhoid fever. We identified specific carbohydrate moieties on specific surface glycoproteins that serve as receptors for typhoid toxin, which explains its broad cell target specificity. We present the atomic structure of typhoid toxin, which shows an unprecedented A(2)B(5) organization with two covalently-linked A subunits non-covalently-associated to a pentameric B subunit. The structure provides insight into the toxin’s receptor-binding specificity and delivery mechanisms and reveals how the activities of two powerful toxins have been coopted into a single, unique toxin that can induce many of the symptoms characteristic of typhoid fever. These findings may lead to the development of potentially life-saving therapeutics against typhoid fever. 2013-07-10 2013-07-18 /pmc/articles/PMC4144355/ /pubmed/23842500 http://dx.doi.org/10.1038/nature12377 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Song, Jeongmin Gao, Xiang Galán, Jorge E. Conferring Virulence: Structure and Function of the chimeric A(2)B(5) Typhoid Toxin |
title | Conferring Virulence: Structure and Function of the chimeric A(2)B(5) Typhoid Toxin |
title_full | Conferring Virulence: Structure and Function of the chimeric A(2)B(5) Typhoid Toxin |
title_fullStr | Conferring Virulence: Structure and Function of the chimeric A(2)B(5) Typhoid Toxin |
title_full_unstemmed | Conferring Virulence: Structure and Function of the chimeric A(2)B(5) Typhoid Toxin |
title_short | Conferring Virulence: Structure and Function of the chimeric A(2)B(5) Typhoid Toxin |
title_sort | conferring virulence: structure and function of the chimeric a(2)b(5) typhoid toxin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144355/ https://www.ncbi.nlm.nih.gov/pubmed/23842500 http://dx.doi.org/10.1038/nature12377 |
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