Heat-Stable Enterotoxins of Enterotoxigenic  Escherichia coli  and Their Impact on Host Immunity

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Abstract

Enterotoxigenic Escherichia coli (ETEC) are an important diarrhea-causing pathogen and are regarded as a global threat for humans and farm animals. ETEC possess several virulence factors to infect its host, including colonization factors and enterotoxins. Production of heat-stable enterotoxins (STs) by most ETEC plays an essential role in triggering diarrhea and ETEC pathogenesis. In this review, we summarize the heat-stable enterotoxins of ETEC strains from different species as well as the molecular mechanisms used by these heat-stable enterotoxins to trigger diarrhea. As recently described, intestinal epithelial cells are important modulators of the intestinal immune system. Thus, we also discuss the impact of the heat-stable enterotoxins on this role of the intestinal epithelium and how these enterotoxins might affect intestinal immune cells. Finally, the latest developments in vaccination strategies to protect against infections with ST secreting ETEC strains are discussed. This review might inform and guide future research on heat-stable enterotoxins to further unravel their molecular pathogenesis, as well as to accelerate vaccine design.

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Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues.

Samuel Lai, Ying-Ying Wang, Justin Hanes (2009)

Mucus is a viscoelastic and adhesive gel that protects the lung airways, gastrointestinal (GI) tract, vagina, eye and other mucosal surfaces. Most foreign particulates, including conventional particle-based drug delivery systems, are efficiently trapped in human mucus layers by steric obstruction and/or adhesion. Trapped particles are typically removed from the mucosal tissue within seconds to a few hours depending on anatomical location, thereby strongly limiting the duration of sustained drug delivery locally. A number of debilitating diseases could be treated more effectively and with fewer side effects if drugs and genes could be more efficiently delivered to the underlying mucosal tissues in a controlled manner. This review first describes the tenacious mucus barrier properties that have precluded the efficient penetration of therapeutic particles. It then reviews the design and development of new mucus-penetrating particles that may avoid rapid mucus clearance mechanisms, and thereby provide targeted or sustained drug delivery for localized therapies in mucosal tissues.

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The impoverished gut--a triple burden of diarrhoea, stunting and chronic disease.

Richard Guerrant, Mark DeBoer, Sean R. Moore … (2013)

More than one-fifth of the world's population live in extreme poverty, where a lack of safe water and adequate sanitation enables high rates of enteric infections and diarrhoea to continue unabated. Although oral rehydration therapy has greatly reduced diarrhoea-associated mortality, enteric infections still persist, disrupting intestinal absorptive and barrier functions and resulting in up to 43% of stunted growth, affecting one-fifth of children worldwide and one-third of children in developing countries. Diarrhoea in children from impoverished areas during their first 2 years might cause, on average, an 8 cm growth shortfall and 10 IQ point decrement by the time they are 7-9 years old. A child's height at their second birthday is therefore the best predictor of cognitive development or 'human capital'. To this 'double burden' of diarrhoea and malnutrition, data now suggest that children with stunted growth and repeated gut infections are also at increased risk of developing obesity and its associated comorbidities, resulting in a 'triple burden' of the impoverished gut. Here, we Review the growing evidence for this triple burden and potential mechanisms and interventions that must be understood and applied to prevent the loss of human potential and unaffordable societal costs caused by these vicious cycles of poverty.

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Morbidity and mortality due to shigella and enterotoxigenic Escherichia coli diarrhoea: the Global Burden of Disease Study 1990–2016

Ibrahim A Khalil, Christopher E Troeger, Brigette F Blacker … (2018)

Summary Background Shigella and enterotoxigenic Escherichia coli (ETEC) are bacterial pathogens that are frequently associated with diarrhoeal disease, and are a significant cause of mortality and morbidity worldwide. The Global Burden of Diseases, Injuries, and Risk Factors study 2016 (GBD 2016) is a systematic, scientific effort to quantify the morbidity and mortality due to over 300 causes of death and disability. We aimed to analyse the global burden of shigella and ETEC diarrhoea according to age, sex, geography, and year from 1990 to 2016. Methods We modelled shigella and ETEC-related mortality using a Bayesian hierarchical modelling platform that evaluates a wide range of covariates and model types on the basis of vital registration and verbal autopsy data. We used a compartmental meta-regression tool to model the incidence of shigella and ETEC, which enforces an association between incidence, prevalence, and remission on the basis of scientific literature, population representative surveys, and health-care data. We calculated 95% uncertainty intervals (UIs) for the point estimates. Findings Shigella was the second leading cause of diarrhoeal mortality in 2016 among all ages, accounting for 212 438 deaths (95% UI 136 979–326 913) and about 13·2% (9·2–17·4) of all diarrhoea deaths. Shigella was responsible for 63 713 deaths (41 191–93 611) among children younger than 5 years and was frequently associated with diarrhoea across all adult age groups, increasing in elderly people, with broad geographical distribution. ETEC was the eighth leading cause of diarrhoea mortality in 2016 among all age groups, accounting for 51 186 deaths (26 757–83 064) and about 3·2% (1·8–4·7) of diarrhoea deaths. ETEC was responsible for about 4·2% (2·2–6·8) of diarrhoea deaths in children younger than 5 years. Interpretation The health burden of bacterial diarrhoeal pathogens is difficult to estimate. Despite existing prevention and treatment options, they remain a major cause of morbidity and mortality globally. Additional emphasis by public health officials is needed on a reduction in disease due to shigella and ETEC to reduce disease burden. Funding Bill & Melinda Gates Foundation.

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Journal ID (nlm-ta): Toxins (Basel)

Journal ID (iso-abbrev): Toxins (Basel)

Journal ID (publisher-id): toxins

Title: Toxins

Publisher: MDPI

ISSN (Electronic): 2072-6651

Publication date (Electronic): 08 January 2019

Publication date Collection: January 2019

Volume: 11

Issue: 1

Electronic Location Identifier: 24

Affiliations

[1 ]Laboratory of Immunology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium; Haixiu.Wang@ 123456UGent.be (H.W.); Eric.Cox@ 123456UGent.be (E.C.)

[2 ]Laboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Heidestraat 19, 9820 Merelbeke, Belgium; Zifu.Zhong@ 123456UGent.be

[3 ]Animal Medical Testing Center, Department of Animal Production, Faculty of Agricultural & Biological Engineering, Jinhua Polytechnic, No. 888 Haitang West Street, Jinhua 321007, China; luoyu@ 123456jhc.cn

Author notes

[* ]Correspondence: B.Devriendt@ 123456UGent.be ; Tel.: +32-9-2647343

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Publisher ID: toxins-11-00024

DOI: 10.3390/toxins11010024

PMC ID: 6356903

PubMed ID: 30626031

SO-VID: 1f816c6a-8e3b-4f44-9cf4-2a6472a29849

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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/).

Heat-Stable Enterotoxins of Enterotoxigenic Escherichia coli and Their Impact on Host Immunity

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Abstract

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Bacterial extracellular vesicles

Most cited references 83

Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues.

The impoverished gut--a triple burden of diarrhoea, stunting and chronic disease.

Morbidity and mortality due to shigella and enterotoxigenic Escherichia coli diarrhoea: the Global Burden of Disease Study 1990–2016

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