Heat-Labile Enterotoxin Promotes<i>Escherichia coli</i>Adherence to Intestinal Epithelial Cells

Johnson, Amber M.; Kaushik, Radhey S.; Francis, David; Fleckenstein, James M.; Hardwidge, Philip R.

doi:10.1128/jb.00822-08

Cited by 82 publications

(99 citation statements)

References 47 publications

(34 reference statements)

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“…Heat-labile toxin has previously been shown to promote epithelial cell adhesion (17) and intestinal colonization (1, 3) by ETEC. Given the association of LT with OMV and the protective effect of these vesicles, we examined whether immunization with LT alone would afford protection against colonization.…”

Section: Resultsmentioning

confidence: 99%

Outer Membrane Vesicles Induce Immune Responses to Virulence Proteins and Protect against Colonization by Enterotoxigenic Escherichia coli

Roy

Hamilton

Munson

et al. 2011

Clin Vaccine Immunol

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Enterotoxigenic Escherichia coli (ETEC) strains are a heterogeneous group of pathogens that produce heat-labile (LT) and/or heat-stable (ST) enterotoxins. Collectively, these pathogens are responsible for hundreds of thousands of deaths annually in developing countries, particularly in children under the age of 5 years. The heterogeneity of previously investigated molecular targets and the lack of complete sustained protection afforded by antitoxin immunity have impeded progress to date toward a broadly protective vaccine. Many pathogens, including ETEC, have the capacity to form outer membrane vesicles (OMV), which often contain one or more virulence proteins. Prompted by recent studies that identified several immunogenic virulence proteins in outer membrane vesicles of ETEC, we sought to examine the immunogenicity and protective efficacy of these structures in a murine model of infection. Here we demonstrate that immunization with OMV impairs ETEC colonization of the small intestine and stimulates antibodies that recognize the heat-labile toxin and two additional putative virulence proteins, the EtpA adhesin and CexE. Similar to earlier studies with EtpA, vaccination with LT alone also inhibited intestinal colonization. Together, these findings suggest that OMV could be exploited to deliver protective antigens relevant to development of ETEC vaccines.Enterotoxigenic Escherichia coli (ETEC) strains are a diverse group of diarrheal pathogens that share the ability to colonize the small intestine, where they produce heat-labile (LT) and/or heat-stable (ST) enterotoxins. These organisms are a leading cause of diarrhea in developing countries, where they are responsible for an estimated 300,000 to 500,000 deaths per year, mostly in young children (33).Unfortunately, there is no broadly protective vaccine available to prevent these infections (5). Although plasmid-encoded colonization factors (CFs) have been a major focus of vaccine development efforts for ETEC to date, the underlying plasticity of E. coli genomes (25) and the antigenic heterogeneity of CFs (5) have impeded vaccine strategies based solely on these antigens. Additional approaches that incorporate highly conserved molecular targets are therefore needed to focus future endeavors toward the design of effective vaccines.Recent immunoproteomic studies (27) identified a number of known and putative ETEC virulence factors associated with outer membrane vesicles (OMV), small spherical "blebs" released from the surfaces of E. coli and other . Given the established association of LT with OMV (16) and the potential utility of vesicle-based vaccines (4, 14, 31), we elected to examine the immunogenicity and protective efficacy of ETEC-derived OMV in an animal model of ETEC infection. MATERIALS AND METHODS Bacterial strains and plasmids.A complete list of bacterial strains and recombinant expression plasmids used in these experiments is included in Table 1.Preparation of outer membrane vesicles. Vesicles were prepared from culture supernatants of either strain H10...

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Section: Resultsmentioning

confidence: 99%

Outer Membrane Vesicles Induce Immune Responses to Virulence Proteins and Protect against Colonization by Enterotoxigenic Escherichia coli

Roy

Hamilton

Munson

et al. 2011

Clin Vaccine Immunol

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“…(CFTR: cystic fibrosis transmembrane conductance regulator) e impide la absorción del intestino y de esta forma ocasiona diarrea secretora de amplia intensidad 77 (Figura 3). En las ST, la unión está mediada por la guanilato-ciclasa-C (GC-C) y existe un aumento del GMP cíclico dependiente de la proteína quinasa II donde se produce el mismo efecto de la LT al aumentar la secreción por el CFTR 78 .…”

Section: Patogeniaunclassified

Mecanismos de virulencia de Escherichia coli enteropatógena

Farfán-García¹,

Ariza-Rojas²,

Vargas-Cárdenas³

et al. 2016

Rev. chil. infectol.

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“…As discussed in reference 748, LT has also been shown to interact with lipid A of LPS (association with OMVs), blood type A sugars, and non-GM1 gangliosides, albeit at lower affinities. Additional roles have been characterized for LT, including contributing to adherence to host cells through activation of host signaling pathways (750,751), as well as suppression of antimicrobial peptide expression (752).…”

Section: Pathogenesismentioning

confidence: 99%

Recent Advances in Understanding Enteric Pathogenic Escherichia coli

et al. 2013

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SUMMARY Although Escherichia coli can be an innocuous resident of the gastrointestinal tract, it also has the pathogenic capacity to cause significant diarrheal and extraintestinal diseases. Pathogenic variants of E. coli (pathovars or pathotypes) cause much morbidity and mortality worldwide. Consequently, pathogenic E. coli is widely studied in humans, animals, food, and the environment. While there are many common features that these pathotypes employ to colonize the intestinal mucosa and cause disease, the course, onset, and complications vary significantly. Outbreaks are common in developed and developing countries, and they sometimes have fatal consequences. Many of these pathotypes are a major public health concern as they have low infectious doses and are transmitted through ubiquitous mediums, including food and water. The seriousness of pathogenic E. coli is exemplified by dedicated national and international surveillance programs that monitor and track outbreaks; unfortunately, this surveillance is often lacking in developing countries. While not all pathotypes carry the same public health profile, they all carry an enormous potential to cause disease and continue to present challenges to human health. This comprehensive review highlights recent advances in our understanding of the intestinal pathotypes of E. coli .

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Heat-Labile Enterotoxin PromotesEscherichia coliAdherence to Intestinal Epithelial Cells

Cited by 82 publications

References 47 publications

Outer Membrane Vesicles Induce Immune Responses to Virulence Proteins and Protect against Colonization by Enterotoxigenic Escherichia coli

Outer Membrane Vesicles Induce Immune Responses to Virulence Proteins and Protect against Colonization by Enterotoxigenic Escherichia coli

Mecanismos de virulencia de Escherichia coli enteropatógena

Recent Advances in Understanding Enteric Pathogenic Escherichia coli

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