This book presents an overview of Shiga toxin-producing E. coli (STEC), with in-depth coverage of key areas such as recent Shiga toxin-related poisonings in Europe and the US, the structure, production, and mechanism of action of Shiga toxin, and current methods of detection. The globalization of food production has introduced new risk factors and intensified existing hazards, complicating the assurance of food safety. Foodborne illness outbreaks, such as those related to STEC, are becoming more common and more dangerous. The threat that these bacterial toxins pose to the food supply is magnified by the frequent occurrence and severity of Shiga toxin-caused disease. As a result, STEC and their toxins remain a primary concern in food safety. This review serves as a key resource for scientists in the field and public health and regulatory officials charged with maintaining food safety. This book also looks to the future of treatment of Shiga toxin-associated disease, specificall
y the translation of lab bench science into clinical therapeutic strategies.
1. Outbreaks of Shiga toxin-related poisoning An overview of the numerous major outbreaks of Shiga toxin related poisonings that have occurred in the United States and Europe, including - the early outbreaks at McDonalds in 1982, the infamous Jack in the Box outbreak in 1993 - the European outbreak associated with fresh sprouts in 2013 - 9 outbreaks associated with spinach or lettuce from the Salinas Valley of California"s central coast. 2. Structure of Shiga toxins -- a complex structure and mechanism of action -- six subunits, five identical binding units and one catalytic unit that is responsible for the toxicity -- relationship between Shiga toxins and other AB5 toxins -- subtypes of Shiga toxins and new variants that have recently emerged. 3. Mechanism of action -- the phage biology that controls the production of the toxins -- translocation of toxin to sites of action -- toxin action at the cellular and molecular level. 4. Significant threats to human health -- impact o
f antibiotics and antibiotic resistance on STEC disease -- intoxication with more than one toxin -- sequellae of STEC-provoked disease. 5. Methods for detection of Shiga toxins-- classical animal bioassay -- immunoassay, including ELISA and solid and bead array systems -- cell-based methods -- indirect PCR-based methods -- instrumental methods, including mass spectrometry, for directly detecting these toxins. 6. Conclusions and a glimpse into the future -- a significant and growing threat to human health and food biosecurity -- translation of lab bench science into clinical treatments for STEC disease.
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1 | (4) |
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4 | (1) |
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2 Outbreaks of Shiga Toxin-Related Poisoning |
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5 | (16) |
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2.1 Human and Economic Impacts of STEC Outbreaks |
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5 | (3) |
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2.2 Effectiveness of STEC in Causing Severe Disease Outbreaks |
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8 | (1) |
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2.3 History of STEC Outbreaks and Their Continuing Evolution |
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8 | (4) |
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2.4 Less Common Sources of STEC Outbreaks |
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12 | (9) |
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14 | (7) |
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3 Structure of Shiga Toxins and Other AB5 Toxins |
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21 | (26) |
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3.1 Structure of Shiga Toxins |
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21 | (3) |
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3.2 Production, Activity, and Gene Structure |
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24 | (4) |
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3.3 Binding to Sugars of Gangliosides |
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28 | (2) |
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3.4 Entry to Cells and Intracellular Trafficking |
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30 | (3) |
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3.5 Toxicity Differences Among Shiga Toxin Types and Subtypes |
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33 | (2) |
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3.6 Other AB5 Protein Toxins |
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35 | (12) |
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38 | (9) |
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4 Regulation of Shiga Toxin Production |
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47 | (16) |
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47 | (3) |
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4.2 Mobile Genetic Elements in E. coli: Transposons and Integrons |
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50 | (1) |
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4.3 Phage Control of Shiga Toxin Production |
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51 | (4) |
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4.4 Impacts of Phages and Mobile Elements on Pathogenicity |
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55 | (8) |
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58 | (5) |
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5 Significant Threats to Human Health |
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63 | (14) |
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5.1 Diverse Health Threats: Bacterial Species and Toxin Types, Subtypes, and Variants |
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63 | (2) |
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5.2 Other Virulence Factors |
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65 | (1) |
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5.3 Shiga Toxin Binding Sites: Host Cell Gangliosides |
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66 | (1) |
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5.4 Development of Serious Sequelae of STEC Infection |
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67 | (1) |
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5.5 Antibiotics in Treatment of Shiga Toxin-Associated Disease |
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68 | (1) |
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5.6 Variations in Disease Associated with Stx Type and Subtype |
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69 | (1) |
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5.7 Inferences from PCR Data |
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70 | (7) |
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72 | (5) |
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6 Detection Methods for Shiga Toxins and Shiga Toxin-Producing E. coli |
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77 | (24) |
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6.1 The Context and the Use of Culture Methods, Nucleic Acid Methods, and Immunoassays for STEC |
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77 | (4) |
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6.2 Detection of Shiga Toxins by Bioassay: Animals, Cells, and Receptors |
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81 | (2) |
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6.3 Structure-Based Assays for Stx: General Considerations and ELISAs Using Polyclonal Antibodies |
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83 | (3) |
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6.4 Monoclonal Antibodies for Stx Detection, Inactivation, and Protection |
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86 | (1) |
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6.5 Monoclonal Antibodies for Differentiating Stx Subtypes |
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87 | (1) |
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6.6 Special-Purpose Immunoassay Methods: Amplification, Portability, and Arrays |
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88 | (3) |
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6.7 Mass Spectrometric Methods for Detecting Shiga Toxins |
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91 | (10) |
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94 | (7) |
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7 Conclusions and a Glimpse into the Future |
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101 | (14) |
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7.1 Exploiting Shiga Toxins for Beneficial Uses |
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101 | (1) |
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7.2 Future Strategies to Treat and Prevent Shiga Toxin-Related Disease |
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102 | (5) |
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107 | (8) |
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109 | (6) |
| Index |
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115 | |
Dr. Christopher J. Silva is a Research Chemist for the USDA-ARS at the Western Regional Research Center in Albany, California. He earned a Ph.D. degree in organic chemistry from Stanford University. His active area of research uses mass spectrometry to detect and quantify proteins, including Shiga toxins, other protein toxins and prions. He has authored or co-authored 70 scientific publications including peer reviewed papers, invited book chapters, proceedings and reviews
Dr. David L. Brandon received an A.B. from Harvard College and Ph.D. in biochemistry from Harvard University (Cambridge, MA, USA). He retired in 2016, after 37 years as Research Chemist with the USDA Agricultural Research Service, and has served in leadership and editorial positions in the field of analytical food safety. He is recognized for his research in the areas of toxins and anti-nutrients in food and feed and immunoanalysis of foodborne contaminants, including bacterial pathogens and drug and pesticide residues. His work has involved significant international collaborations, with applications to food safety, crop improvement, and food defense. Dr. Brandon is author/inventor of over 80 publications and patents, with several technologies licensed to industry.
Dr. Craig B. Skinner attended the University of California, San Diego to receive his B.S. in Biochemistry before attending the University of California, Davis for his Ph.D in Biochemistry and Molecular Biology. He worked at the USDA for 5 years as a postdoctoral molecular biologist in the lab of Dr. Xiaohua He. He is currently employed by DiCE Molecules, LLC (Redwood City, CA). During his postdoctoral tenure, Dr. Skinner developed purification procedures and molecular tools for detection of toxins, particularly the Shiga toxins. He is the primary author or co-author of 13 papers in the food safety field and co-inventor of patented and licensed technology for Stx2f subtype-specific antibodies.
Dr. Xiaohua He is a Research Molecular Biologist in the Foodborne Toxin Detection and Prevention Research Unit at the Western Regional Research Center, USDA Agricultural Research Service, Albany, California. She received her Ph.D. in Plant Pathology from the University of California, Riverside, and had postdoctoral experience at Purdue and Cornell Universities. Her research focuses on development of molecular tools for sensitive detection of zoonotic pathogens and toxins in food, and environmental and clinical samples; investigation of toxin synthesis and novel mechanisms of host cell injury; and toxicokinetics. The 2015 Federal Laboratory Consortium, Far West Region, Outstanding Technology Development Award recognized her contribution to Improved Detection of Shiga Toxin through Monoclonal Antibodies. She is active in editorial positions and international collaborations, andis author/inventor of over 70 publications and patents, with 14 technologies licensed to industry.
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