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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-7022315 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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