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

Abstract

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 publicmore » risk of infection by less-known STECs.« less

Authors:
 [1]; ORCiD logo [1];  [2];  [2];  [2];  [2];  [3];  [1]
  1. United States Department of Agriculture, Albany, CA (United States)
  2. Chinese Center for Disease Control and Prevention, Beijing (China)
  3. Argonne National Lab. (ANL), Lemont, IL (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
U.S. Department of Agriculture (USDA); USDOE Office of Science (SC)
OSTI Identifier:
1647158
Grant/Contract Number:  
AC02-06CH11357
Resource Type:
Accepted Manuscript
Journal Name:
Microorganisms
Additional Journal Information:
Journal Volume: 8; Journal Issue: 1; Journal ID: ISSN 2076-2607
Publisher:
MDPI
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Crystal structure; cytotoxicity; Shiga toxin; Gb3 and Gb4 receptors; immunoassays; neutralization; STEC; toxin stability

Citation Formats

Hughes, Anna C., Zhang, Yuzhu, Bai, Xiangning, Xiong, Yanwen, Wang, Yan, Yang, Xi, Xu, Qingping, and He, Xiaohua. Structural and Functional Characterization of Stx2k, a New Subtype of Shiga Toxin 2. United States: N. p., 2019. Web. https://doi.org/10.3390/microorganisms8010004.
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. United States. https://doi.org/10.3390/microorganisms8010004
Hughes, Anna C., Zhang, Yuzhu, Bai, Xiangning, Xiong, Yanwen, Wang, Yan, Yang, Xi, Xu, Qingping, and He, Xiaohua. Wed . "Structural and Functional Characterization of Stx2k, a New Subtype of Shiga Toxin 2". United States. https://doi.org/10.3390/microorganisms8010004. https://www.osti.gov/servlets/purl/1647158.
@article{osti_1647158,
title = {Structural and Functional Characterization of Stx2k, a New Subtype of Shiga Toxin 2},
author = {Hughes, Anna C. and Zhang, Yuzhu and Bai, Xiangning and Xiong, Yanwen and Wang, Yan and Yang, Xi and Xu, Qingping and He, Xiaohua},
abstractNote = {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.},
doi = {10.3390/microorganisms8010004},
journal = {Microorganisms},
number = 1,
volume = 8,
place = {United States},
year = {2019},
month = {12}
}

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