|BIERNBAUM, ERIKA - Oak Ridge Institute For Science And Education (ORISE)
Submitted to: Toxins
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/22/2021
Publication Date: 1/16/2022
Citation: Biernbaum, E.N., Kudva, I.T. 2022. AB5 Enterotoxin-Mediated Pathogenesis: Perspectives gleaned from Shiga toxins. Toxins. 14(1). Article 62. https://doi.org/10.3390/toxins14010062.
Interpretive Summary: Bacterial foodborne pathogens that can infect humans and cause disease ranging from watery diarrhea to organ failures, and toxins are produced by many foodborne pathogens. The structure and mechanism of action of toxins differs between pathogens and this in turn affects disease outcomes. One such toxin is the Shiga toxin produced by Shiga toxin-producing Escherichia coli or STEC. STEC are carried by cattle, who remain disease-free, but STEC can cause severe disease in humans after unintentional ingestion, commonly through food products. Different forms of Shiga toxin that have varying host and host-cell binding affinities have been identified among STEC. This review provides a comprehensive overview of Shiga toxin in the context of related toxins produced by other non-STEC pathogens in addition to summarizing the role of Shiga toxins in disease, detection, and possible therapeutic options.
Technical Abstract: Foodborne diseases affect an estimated 600 million people worldwide annually, with majority of these illnesses caused by Norovirus, Vibrio, Listeria, and members of the Enterobacteriaceae family such as Campylobacter, Salmonella, and Escherichia coli. To elicit such infections in humans, bacterial pathogens express a combination of virulence factors and toxins. AB5 toxins are an example of such toxins that can cause various clinical manifestations including dehydration, diarrhea, kidney damage, hemorrhagic colitis, and hemolytic uremic syndrome (HUS). Treatment of most bacterial foodborne illnesses consists of fluid replacement and antibiotics. However, antibiotics are not recommended for infections caused by Shiga toxin-producing E. coli (STEC) because of the increased risk of HUS development, although there are conflicting views and results in this regard. Lack of effective treatment strategies for STEC infections pose a public health threat during outbreaks; therefore, antibiotics that do not induce toxin expression could be further explored, along with antibiotic alternatives for STEC infections. The overall goal of this review is to provide a succinct summary on the mechanisms of action and pathogenesis of AB5 and related toxins, as expressed by Enterobacteriaceae family members, with a primary focus on Shiga toxins (Stx). Role of Stx in human STEC disease, detection methodologies, and available treatment options is also briefly discussed.