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Structural and Functional Characterization of Stx2k, a New Subtype of Shiga Toxin 2

Shiga toxin (Stx) is the major virulence factor of Shiga toxin-producing Escherichia coli (STEC). Stx evolves rapidly and, as such, new subtypes continue to emerge that challenge the efficacy of existing disease management and surveillance strategies. A new subtype, Stx2k, was recently identified in...

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Autores principales: Hughes, Anna C., Zhang, Yuzhu, Bai, Xiangning, Xiong, Yanwen, Wang, Yan, Yang, Xi, Xu, Qingping, He, Xiaohua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022315/
https://www.ncbi.nlm.nih.gov/pubmed/31861375
http://dx.doi.org/10.3390/microorganisms8010004
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author Hughes, Anna C.
Zhang, Yuzhu
Bai, Xiangning
Xiong, Yanwen
Wang, Yan
Yang, Xi
Xu, Qingping
He, Xiaohua
author_facet Hughes, Anna C.
Zhang, Yuzhu
Bai, Xiangning
Xiong, Yanwen
Wang, Yan
Yang, Xi
Xu, Qingping
He, Xiaohua
author_sort Hughes, Anna C.
collection PubMed
description Shiga toxin (Stx) is the major virulence factor of Shiga toxin-producing Escherichia coli (STEC). Stx evolves rapidly and, as such, new subtypes continue to emerge that challenge the efficacy of existing disease management and surveillance strategies. A new subtype, Stx2k, was recently identified in E. coli isolated from a wide range of sources including diarrheal patients, animals, and raw meats, and was poorly detected by existing immunoassays. In this study, the structure of Stx2kE167Q was determined at 2.29 Å resolution and the conservation of structure with Stx2a was revealed. A novel polyclonal antibody capable of neutralizing Stx2k and an immunoassay, with a 10-fold increase in sensitivity compared to assays using extant antibodies, were developed. Stx2k is less toxic than Stx2a in Vero cell assays but is similar to Stx2a in receptor-binding preference, thermostability, and acid tolerance. Although Stx2k does not appear to be as potent as Stx2a to Vero cells, the wide distribution and blended virulence profiles of the Stx2k-producing strains suggest that horizontal gene transfer through Stx2k-converting phages could result in the emergence of new and highly virulent pathogens. This study provides useful information and tools for early detection and control of Stx2k-producing E. coli, which could reduce public risk of infection by less-known STECs.
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spelling pubmed-70223152020-03-09 Structural and Functional Characterization of Stx2k, a New Subtype of Shiga Toxin 2 Hughes, Anna C. Zhang, Yuzhu Bai, Xiangning Xiong, Yanwen Wang, Yan Yang, Xi Xu, Qingping He, Xiaohua Microorganisms Article Shiga toxin (Stx) is the major virulence factor of Shiga toxin-producing Escherichia coli (STEC). Stx evolves rapidly and, as such, new subtypes continue to emerge that challenge the efficacy of existing disease management and surveillance strategies. A new subtype, Stx2k, was recently identified in E. coli isolated from a wide range of sources including diarrheal patients, animals, and raw meats, and was poorly detected by existing immunoassays. In this study, the structure of Stx2kE167Q was determined at 2.29 Å resolution and the conservation of structure with Stx2a was revealed. A novel polyclonal antibody capable of neutralizing Stx2k and an immunoassay, with a 10-fold increase in sensitivity compared to assays using extant antibodies, were developed. Stx2k is less toxic than Stx2a in Vero cell assays but is similar to Stx2a in receptor-binding preference, thermostability, and acid tolerance. Although Stx2k does not appear to be as potent as Stx2a to Vero cells, the wide distribution and blended virulence profiles of the Stx2k-producing strains suggest that horizontal gene transfer through Stx2k-converting phages could result in the emergence of new and highly virulent pathogens. This study provides useful information and tools for early detection and control of Stx2k-producing E. coli, which could reduce public risk of infection by less-known STECs. MDPI 2019-12-18 /pmc/articles/PMC7022315/ /pubmed/31861375 http://dx.doi.org/10.3390/microorganisms8010004 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hughes, Anna C.
Zhang, Yuzhu
Bai, Xiangning
Xiong, Yanwen
Wang, Yan
Yang, Xi
Xu, Qingping
He, Xiaohua
Structural and Functional Characterization of Stx2k, a New Subtype of Shiga Toxin 2
title Structural and Functional Characterization of Stx2k, a New Subtype of Shiga Toxin 2
title_full Structural and Functional Characterization of Stx2k, a New Subtype of Shiga Toxin 2
title_fullStr Structural and Functional Characterization of Stx2k, a New Subtype of Shiga Toxin 2
title_full_unstemmed Structural and Functional Characterization of Stx2k, a New Subtype of Shiga Toxin 2
title_short Structural and Functional Characterization of Stx2k, a New Subtype of Shiga Toxin 2
title_sort structural and functional characterization of stx2k, a new subtype of shiga toxin 2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022315/
https://www.ncbi.nlm.nih.gov/pubmed/31861375
http://dx.doi.org/10.3390/microorganisms8010004
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