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Special Issue "Enterotoxigenic Escherichia coli Infection and Vaccine-Mediated Immunity"

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A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Molecular Microbiology and Immunology".

Deadline for manuscript submissions: 30 December 2023 | Viewed by 2507

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Special Issue Editors

Dr. Frederick J. Cassels

E-Mail Website
Guest Editor

PATH Center for Vaccine Innovation and Access, Seattle, WA, USA
Interests: enteric bacterial and viral vaccines; COVID-19 vaccines; molecular mediators of microbial adherence

Dr. August Louis Bourgeois

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Guest Editor

PATH Center for Vaccine Innovation and Access, Washington, DC, USA
Interests: ETEC epidemiology; immunology; vaccines

Prof. Dr. James M. Fleckenstein

E-Mail Website
Guest Editor

Department of Medicine, Division of Infectious Diseases, Washington University in Saint Louis, School of Medicine, Saint Louis, MO, USA
Interests: enterotoxigenic E. coli (ETEC); vaccines; pathogen–host interactions

Dr. Firdausi Qadri

E-Mail Website
Guest Editor

1. Programme for Enteric and Respiratory Infections, Infectious Diseases Division, icddr,b, Dhaka 1212, Bangladesh
2. Lead, Institute for Developing Science and Health Initiatives (ideSHi), Dhaka, Bangladesh
Interests: immunology and molecular genomics of enteric and respiratory infections, including COVID-19 infections in LMICs; vaccine evaluation in endemic settings

Dr. Richard I. Walker

E-Mail Website
Guest Editor

PATH Center for Vaccine Innovation and Access, Washington, DC, USA
Interests: ETEC; vaccine development; immunology; model development

Special Issue Information

Dear Colleagues,

Enterotoxigenic Escherichia coli (ETEC) is the most prevalent bacterial pathogen causing acute watery diarrhea in young children in low- and middle-income Countries (LMICs). The high ETEC burden results in children facing numerous diarrhea episodes, which potentially contributes to poor growth and cogntivie development. ETEC also remains the leading cause of diarrhea in travelers and military visiting endemic areas. The WHO recently re-affirmed ETEC as a vaccine priority and, given its recogncition as a signficant AMR threat, public health stakeholders have urged that the development for a vaccine be accelerated.

The aim of this Special Issue of Microorganisms is to present articles that provide an in-depth look at the current state of ETEC vaccines and the supportive information necessary to advance these vaccines to licensure. Topics:

Assessment of the value of vaccines;
Epidemiology and global burden;
Host parameters and genomics that predict responses;
Application of new omics technologies for the characterization of host responses;
Preclinical evaluation of vaccine candidates and models of disease;
Vaccine candidates in clinical trials and in human challenge models.

It is expected that this Special Issue of Microorganisms will accelerate the field toward an ETEC vaccine(s) licensure so the negative impact of this insidious disease can be minimized as soon as possible.

Dr. Frederick J. Cassels
Dr. August Louis Bourgeois
Prof. Dr. James M. Fleckenstein
Dr. Firdausi Qadri
Dr. Richard I. Walker
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

enterotoxigenic Eschericia coli
colonization factors
non-canonical antigens
ETEC genomics and proteomics
ETEC vaccines
ETEC human challenge model
ETEC animal models
preclinical evaluation ETEC vaccines
host parameters ETEC vaccines
mucosal and systemic ETEC immunity

Published Papers (4 papers)

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Research

Open AccessArticle

Seroprevalence Study of Conserved Enterotoxigenic Escherichia coli Antigens in Globally Diverse Populations

Frederick Matthew Kuhlmann

Sherlie Jean Louis Dulience

and

James M. Fleckenstein

Microorganisms 2023, 11(9), 2221; https://doi.org/10.3390/microorganisms11092221 - 31 Aug 2023

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Abstract

Enterotoxigenic Escherichia coli (ETEC) are common causes of infectious diarrhea among young children of low-and middle-income countries (LMICs) and travelers to these regions. Despite their significant contributions to the morbidity and mortality associated with childhood and traveler’s diarrhea, no licensed vaccines are available. Current vaccine strategies may benefit from the inclusion of additional conserved antigens, which may contribute to broader coverage and enhanced efficacy, given their key roles in facilitating intestinal colonization and effective enterotoxin delivery. EatA and EtpA are widely conserved in diverse populations of ETEC, but their immunogenicity has only been studied in controlled human infection models and a population of children in Bangladesh. Here, we compared serologic responses to EatA, EtpA and heat-labile toxin in populations from endemic regions including Haitian children and subjects residing in Egypt, Cameroon, and Peru to US children and adults where ETEC infections are sporadic. We observed elevated IgG and IgA responses in individuals from endemic regions to each of the antigens studied. In a cohort of Haitian children, we observed increased immune responses following exposure to each of the profiled antigens. These findings reflect the wide distribution of ETEC infections across multiple endemic regions and support further evaluation of EatA and EtpA as candidate ETEC vaccine antigens. Full article

(This article belongs to the Special Issue Enterotoxigenic Escherichia coli Infection and Vaccine-Mediated Immunity)

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Open AccessArticle

Heat-Labile Enterotoxin Decreases Macrophage Phagocytosis of Enterotoxigenic Escherichia coli

and

Microorganisms 2023, 11(8), 2121; https://doi.org/10.3390/microorganisms11082121 - 21 Aug 2023

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Abstract

Enterotoxigenic E. coli (ETEC) are endemic in low-resource settings and cause robust secretory diarrheal disease in children less than five years of age. ETEC cause secretory diarrhea by producing the heat-stable (ST) and/or heat-labile (LT) enterotoxins. Recent studies have shown that ETEC can be carried asymptomatically in children and adults, but how ETEC subvert mucosal immunity to establish intestinal residency remains unclear. Macrophages are innate immune cells that can be exploited by enteric pathogens to evade mucosal immunity, so we interrogated the ability of ETEC and other E. coli pathovars to survive within macrophages. Using gentamicin protection assays, we show that ETEC H10407 is phagocytosed more readily than other ETEC and non-ETEC isolates. Furthermore, we demonstrate that ETEC H10407, at high bacterial burdens, causes nitrite accumulation in macrophages, which is indicative of a proinflammatory macrophage nitric oxide killing response. However, at low bacterial burdens, ETEC H10407 remains viable within macrophages for an extended period without nitrite accumulation. We demonstrate that LT, but not ST, intoxication decreases the number of ETEC phagocytosed by macrophages. Furthermore, we now show that macrophages exposed simultaneously to LPS and LT produce IL-33, which is a cytokine implicated in promoting macrophage alternative activation, iron recycling, and intestinal repair. Lastly, iron restriction using deferoxamine induces IL-33 receptor (IL-33R) expression and allows ETEC to escape macrophages. Altogether, these data demonstrate that LT provides ETEC with the ability to decrease the perceived ETEC burden and suppresses the initiation of inflammation. Furthermore, these data suggest that host IL-33/IL-33R signaling may augment pathways that promote iron restriction to facilitate ETEC escape from macrophages. These data could help explain novel mechanisms of immune subversion that may contribute to asymptomatic ETEC carriage. Full article

(This article belongs to the Special Issue Enterotoxigenic Escherichia coli Infection and Vaccine-Mediated Immunity)

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Open AccessArticle

The Immunogenicity and Properties of a Whole-Cell ETEC Vaccine Inactivated with Psoralen and UVA Light in Comparison to Formalin

and

Microorganisms 2023, 11(8), 2040; https://doi.org/10.3390/microorganisms11082040 - 09 Aug 2023

Viewed by 733

Abstract

Inactivated whole-cell vaccines present a full repertoire of antigens to the immune system. Formalin treatment, a standard method for microbial inactivation, can modify or destroy protein antigenic epitopes. We tested the hypothesis that photochemical inactivation with psoralen and UVA light (PUVA), which targets nucleic acid, would improve the immunogenicity of an Enterotoxigenic E. coli (ETEC) vaccine relative to a formalin-inactivated counterpart. Exposure of ETEC H10407 to PUVA using the psoralen drug 4′-Aminomethyltrioxsalen hydrochloride (AMT) yielded replication-incompetent bacteria that retained their metabolic activity. CFA/I-mediated mannose-resistant hemagglutination (MRHA) was equivalent for PUVA-inactivated and live ETEC, but was severely reduced for formalin–ETEC, indicating that PUVA preserved fimbrial protein functional integrity. The immunogenicity of PUVA–ETEC and formalin–ETEC was compared in mice ± double mutant heat-labile enterotoxin (dmLT) adjuvant. Two weeks after an intramuscular prime/boost, serum anti-ETEC IgG titers were similar for the two vaccines and were increased by dmLT. However, the IgG responses raised against several conserved ETEC proteins were greater after vaccination with PUVA–ETEC. In addition, PUVA–ETEC generated IgG specific for heat-labile toxin (LT) in the absence of dmLT, which was not a property of formalin–ETEC. These data are consistent with PUVA preserving ETEC protein antigens in their native-like form and justify the further testing of PUVA as a vaccine platform for ETEC using murine challenge models. Full article

(This article belongs to the Special Issue Enterotoxigenic Escherichia coli Infection and Vaccine-Mediated Immunity)

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Open AccessArticle

Reduced Plasma Guanylin Levels Following Enterotoxigenic Escherichia coli-Induced Diarrhea

Ingeborg Brønstad

Hilde Løland von Volkmann

Sunniva Todnem Sakkestad

Hans Steinsland

and

Kurt Hanevik

Microorganisms 2023, 11(8), 1997; https://doi.org/10.3390/microorganisms11081997 - 03 Aug 2023

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Abstract

The intestinal peptide hormones guanylin (GN) and uroguanylin (UGN) interact with the epithelial cell receptor guanylate cyclase C to regulate fluid homeostasis. Some enterotoxigenic Escherichia coli (ETEC) produce heat-stable enterotoxin (ST), which induces diarrhea by mimicking GN and UGN. Plasma concentrations of prohormones of GN (proGN) and UGN (proUGN) are reportedly decreased during chronic diarrheal diseases. Here we investigate whether prohormone concentrations also drop during acute diarrhea caused by ST-producing ETEC strains TW10722 and TW11681. Twenty-one volunteers were experimentally infected with ETEC. Blood (n = 21) and urine (n = 9) specimens were obtained immediately before and 1, 2, 3, and 7 days after ETEC ingestion. Concentrations of proGN and proUGN were measured by ELISA. Urine electrolyte concentrations were measured by photometry and mass spectrometry. Ten volunteers developed diarrhea (D group), and eleven did not (ND group). In the D group, plasma proGN, but not proUGN, concentrations were substantially reduced on days 2 and 3, coinciding with one day after diarrhea onset. No changes were seen in the ND group. ETEC diarrhea also seemed to affect diuresis, the zinc/creatinine ratio, and sodium and chloride secretion levels in urine. ETEC-induced diarrhea causes a reduction in plasma proGN and could potentially be a useful marker for intestinal isotonic fluid loss. Full article

(This article belongs to the Special Issue Enterotoxigenic Escherichia coli Infection and Vaccine-Mediated Immunity)

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