Prevalence of Toxin Types and Colonization Factors in Enterotoxigenic Escherichia coli Isolated during a 2-Year Period from Diarrheal Patients in Bangladesh

2000 ◽  
Vol 38 (1) ◽  
pp. 27-31
Author(s):  
Firdausi Qadri ◽  
Swadesh Kumar Das ◽  
A. S. G. Faruque ◽  
George J. Fuchs ◽  
M. John Albert ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Severe Disease ◽  
Surface Antigens ◽  
Enterotoxigenic Escherichia Coli ◽  
Colonization Factor ◽  
Heat Stable ◽  
Routine Surveillance ◽  
Stool Samples ◽  
Colonization Factors ◽  
Severity Of The Disease

ABSTRACT The prevalence of toxin types and colonization factors (CFs) of enterotoxigenic Escherichia coli (ETEC) was prospectively studied with fresh samples ( n = 4,662) obtained from a 2% routine surveillance of diarrheal stool samples over 2 years, from September 1996 to August 1998. Stool samples were tested by enzyme-linked immunoassay techniques and with specific monoclonal antibodies for the toxins and CFs. The prevalence of ETEC was 14% ( n = 662), with over 70% of the strains isolated from children 0 to 5 years of age, of whom 93% were in the 0- to 3-year-old age range. Of the total ETEC isolates, 49.4% were positive for the heat-stable toxin (ST), 25.4% were positive for the heat-labile toxin (LT) only, and 25.2% were positive for both LT and ST. The rate of ETEC isolation peaked in the hot summer months of May to September and decreased in winter. About 56% of the samples were positive for 1 or more of the 12 CFs that were screened for. The coli surface antigens CS4, CS5, and/or CS6 of the colonization factor antigen (CFA)/IV complex were most prevalent (incidence, 31%), followed by CFA/I (23.5%) and coli surface antigens CS1, CS2, and CS3 of CFA/II (21%). In addition, other CFs detected in decreasing order were CS7 (8%), CS14 (PCFO166) (7%), CS12 (PCFO159) (4%), CS17 (3%), and CS8 (CFA/III) (2.7%). The ST- or LT- and ST-positive ETEC isolates expressed the CFs known to be the most prevalent (i.e., CFA/I, CFA/II, and CFA/IV), while the strains positive for LT only did not. Among children who were infected with ETEC as the single pathogen, a trend of relatively more severe disease in children infected with ST-positive ( P < 0.001) or LT- and ST-positive ( P < 0.001) ETEC isolates compared to the severity of the disease in children infected with LT only-positive ETEC isolates was seen. This study supports the fact that ETEC is still a major cause of childhood diarrhea in Bangladesh, especially in children up to 3 years of age, and that measures to prevent such infections are needed in developing countries.

scholarly journals Heat-Stable Enterotoxin of Enterotoxigenic Escherichia coli as a Vaccine Target

2010 ◽  
Vol 78 (5) ◽  
pp. 1824-1831 ◽  
Author(s):  
Arne Taxt ◽  
Rein Aasland ◽  
Halvor Sommerfelt ◽  
James Nataro ◽  
Pål Puntervoll
Keyword(s):  
Escherichia Coli ◽  
Vaccine Development ◽  
Severe Disease ◽  
Epidemiological Data ◽  
Structural Similarity ◽  
Biological Properties ◽  
Cross Reactivity ◽  
Enterotoxigenic Escherichia Coli ◽  
Natural Form ◽  
Heat Stable

ABSTRACT Enterotoxigenic Escherichia coli (ETEC) is responsible for 280 million to 400 million episodes of diarrhea and about 380,000 deaths annually. Epidemiological data suggest that ETEC strains which secrete heat-stable toxin (ST), alone or in combination with heat-labile toxin (LT), induce the most severe disease among children in developing countries. This makes ST an attractive target for inclusion in an ETEC vaccine. ST is released upon colonization of the small intestine and activates the guanylate cyclase C receptor, causing profuse diarrhea. To generate a successful toxoid, ST must be made immunogenic and nontoxic. Due to its small size, ST is nonimmunogenic in its natural form but becomes immunogenic when coupled to an appropriate large-molecular-weight carrier. This has been successfully achieved with several carriers, using either chemical conjugation or recombinant fusion techniques. Coupling of ST to a carrier may reduce toxicity, but further reduction by mutagenesis is desired to obtain a safe vaccine. More than 30 ST mutants with effects on toxicity have been reported. Some of these mutants, however, have lost the ability to elicit neutralizing immune responses to the native toxin. Due to the small size of ST, separating toxicity from antigenicity is a particular challenge that must be met. Another obstacle to vaccine development is possible cross-reactivity between anti-ST antibodies and the endogenous ligands guanylin and uroguanylin, caused by structural similarity to ST. Here we review the molecular and biological properties of ST and discuss strategies for developing an ETEC vaccine that incorporates immunogenic and nontoxic derivatives of the ST toxin.

scholarly journals Construction and Phase I Clinical Evaluation of the Safety and Immunogenicity of a Candidate Enterotoxigenic Escherichia coli Vaccine Strain Expressing Colonization Factor Antigen CFA/I

2006 ◽  
Vol 74 (2) ◽  
pp. 1062-1071 ◽  
Author(s):  
Arthur K. Turner ◽  
Juliet C. Beavis ◽  
Jonathan C. Stephens ◽  
Judith Greenwood ◽  
Cornelia Gewert ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Phase I ◽  
Oral Delivery ◽  
Enterotoxigenic Escherichia Coli ◽  
Virulence Plasmid ◽  
Igg Antibody ◽  
Open Label ◽  
Double Blind ◽  
Colonization Factor ◽  
Heat Stable

ABSTRACT Oral delivery of toxin-negative derivatives of enterotoxigenic Escherichia coli (ETEC) that express colonization factor antigens (CFA) with deletions of the aroC, ompC, ompF, and toxin genes may be an effective approach to vaccination against ETEC-associated diarrhea. We describe the creation and characterization of an attenuated CFA/I-expressing ETEC vaccine candidate, ACAM2010, from a virulent isolate in which the heat-stable enterotoxin (ST) and CFA/I genes were closely linked and on the same virulence plasmid as the enteroaggregative E. coli heat-stable toxin (EAST1) gene. A new suicide vector (pJCB12) was constructed and used to delete the ST and EAST1 genes and to introduce defined deletion mutations into the aroC, ompC, and ompF chromosomal genes. A phase I trial, consisting of an open-label dose escalation phase in 18 adult outpatient volunteers followed by a placebo-controlled double-blind phase in an additional 31 volunteers, was conducted. The vaccine was administered in two formulations, fresh culture and frozen suspension. These were both well tolerated, with no evidence of significant adverse events related to vaccination. Immunoglobulin A (IgA) and IgG antibody-secreting cells specific for CFA/I were assayed by ELISPOT. Positive responses (greater than twofold increase) were seen in 27 of 37 (73%) subjects who received the highest dose level of vaccine (nominally 5 × 109 CFU). Twenty-nine of these volunteers were secreting culturable vaccine organisms at day 3 following vaccination; five were still positive on day 7, with a single isolation on day 13. This live attenuated bacterial vaccine is safe and immunogenic in healthy adult volunteers.

scholarly journals Prospective study of diarrhoeal disease in a cohort of rural Mexican children: incidence and isolated pathogens during the first two years of life

1988 ◽  
Vol 101 (1) ◽  
pp. 123-134 ◽  
Author(s):  
Alejandro Cravioto ◽  
Rosa E. Reyes ◽  
Roberto Ortega ◽  
Guadalupe Fernández ◽  
Raymundo Hernández ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Prospective Study ◽  
Diarrhoeal Disease ◽  
First Year ◽  
Colonization Factor ◽  
Mexican Children ◽  
Heat Stable ◽  
Colonization Factors ◽  
Second Year ◽  
First Year Of Life

SUMMARYColonization of the intestine by putative pathogens was followed longitudinally in a cohort of 56 infants born during one calendar year in a rural Mexican village with faecal cultures taken every fortnight and every time a child had diarrhoea. The frequency of isolation of pathogens during episodes of diarrhoea was compared with that of matched controls from the same cohort. Incidence of diarrhoea during the first year of life was 98%, diminishing to 93% during the second year. The incidence curves for each year were not significantly different (P> 0·1). Isolation of enteropathogenicEscherichia coli, enterotoxigenicEscherichia coliproducing heat-stable (ST) and/or heat-labile (LT) enterotoxins and rotaviruses was significantly higher in infants with diarrhoea during the first 2 years of life. In the case of shigella, although no significant differences were found by semester of life, 13 of 16 children in which these strains were found had diarrhoea. Isolation ofSalmonellaspp.,Campylobacterspp. and protozoa were not significantly different in the two groups during the period studied. Strains showing localized adherence to HEp-2 cells or the presence of colonization factor antigens I or E8775 were found with significantly higher frequency in children with diarrhoea. Eighty-two percent of ST+or LT+ETEC strains isolated produced one of the three known colonization factors.

scholarly journals Importance of Heat-Labile Enterotoxin in Colonization of the Adult Mouse Small Intestine by Human Enterotoxigenic Escherichia coli Strains

2006 ◽  
Vol 74 (2) ◽  
pp. 869-875 ◽  
Author(s):  
Kenneth P. Allen ◽  
Mildred M. Randolph ◽  
James M. Fleckenstein
Keyword(s):  
Escherichia Coli ◽  
Small Intestine ◽  
Diarrheal Disease ◽  
Vaccine Development ◽  
Small Animal ◽  
Enterotoxigenic Escherichia Coli ◽  
Colonization Factor ◽  
Heat Stable ◽  
Heat Labile ◽  
Colonization Factor Antigen I

ABSTRACT Enterotoxigenic Escherichia coli (ETEC) infections are a significant cause of diarrheal disease and infant mortality in developing countries. Studies of ETEC pathogenesis relevant to vaccine development have been greatly hampered by the lack of a suitable small-animal model of infection with human ETEC strains. Here, we demonstrate that adult immunocompetent outbred mice can be effectively colonized with the prototypical human ETEC H10407 strain (colonization factor antigen I; heat-labile and heat-stable enterotoxin positive) and that production of heat-labile holotoxin provides a significant advantage in colonization of the small intestine in this model.

scholarly journals The Major Subunit, CfaB, of Colonization Factor Antigen I from Enterotoxigenic Escherichia coli Is a Glycosphingolipid Binding Protein

2006 ◽  
Vol 74 (6) ◽  
pp. 3488-3497 ◽  
Author(s):  
Lena Jansson ◽  
Joshua Tobias ◽  
Michael Lebens ◽  
Ann-Mari Svennerholm ◽  
Susann Teneberg
Keyword(s):  
Escherichia Coli ◽  
Pathogenic Bacteria ◽  
Binding Capacity ◽  
Enterotoxigenic Escherichia Coli ◽  
E Coli ◽  
Colonization Factor ◽  
Mucosal Surfaces ◽  
Colonization Factors ◽  
Bacteria Adhesion ◽  
Colonization Factor Antigen I

ABSTRACT Bacterial adherence to mucosal surfaces is an important virulence trait of pathogenic bacteria. Adhesion of enterotoxigenic Escherichia coli (ETEC) to the intestine is mediated by a number of antigenically distinct colonization factors (CFs). One of the most common CFs is CFA/I. This has a fimbrial structure composed of a major repeating subunit, CfaB, and a single tip subunit, CfaE. The potential carbohydrate recognition by CFA/I was investigated by binding CFA/I-fimbriated bacteria and purified CFA/I fimbriae to a large number of variant glycosphingolipids separated on thin-layer chromatograms. For both fimbriated bacteria and purified fimbriae, specific interactions could be identified with a number of nonacid glycosphingolipids. These included glucosylceramide, lactosylceramide with phytosphingosine and/or hydroxy fatty acids, neolactotetraosylceramide, gangliotriaosylceramide, gangliotetraosylceramide, the H5 type 2 pentaglycosylceramide, the Lea-5 glycosphingolipid, the Lex-5 glycosphingolipid, and the Ley-6 glycosphingolipid. These glycosphingolipids were also recognized by recombinant E. coli expressing CFA/I in the absence of tip protein CfaE, as well as by purified fimbriae from the same strain. This demonstrates that the glycosphingolipid-binding capacity of CFA/I resides in the major CfaB subunit.

scholarly journals Infection with colonization factor antigen I-expressing enterotoxigenic Escherichia coli boosts antibody responses against heterologous colonization factors in primed subjects

1997 ◽  
Vol 119 (3) ◽  
pp. 391-393 ◽  
Author(s):  
A. RUDIN ◽  
G. WIKLUND ◽  
C. WENNERÅS ◽  
F. QADRI
Keyword(s):  
Escherichia Coli ◽  
Antibody Responses ◽  
Enterotoxigenic Escherichia Coli ◽  
Enzyme Linked Immunosorbent Assay ◽  
Symptomatic Infection ◽  
Colonization Factor ◽  
Serum Iga ◽  
Iga Antibody ◽  
Colonization Factors ◽  
Colonization Factor Antigen I

Enterotoxigenic Escherichia coli (ETEC) adhere to the intestinal mucosa by a number of fimbrial colonization factors (CFs) that have been claimed to induce only type-specific immunity. However, adult Bangladeshi patients infected with CFA/I-expressing bacteria, developed significant plasma IgA antibody responses, as determined by enzyme-linked immunosorbent assay, not only against the homologous fimbriae but also against several heterologous CFs, i.e. CS1, CS2, CS4 and PCFO166 fimbriae. In contrast, North American volunteers, who had probably not been infected by ETEC previously, responded with serum IgA against CFA/I fimbriae but not against any other CFs after symptomatic infection with CFA/I-expressing ETEC. Thus, infection with CFA/I-expressing bacteria may boost immune responses against CFs with a related amino acid sequence in previously primed subjects.

scholarly journals Generation and Characterization of a Live Attenuated Enterotoxigenic Escherichia coli Combination Vaccine Expressing Six Colonization Factors and Heat-Labile Toxin Subunit B

2011 ◽  
Vol 18 (12) ◽  
pp. 2128-2135 ◽  
Author(s):  
Arthur K. Turner ◽  
Jonathan C. Stephens ◽  
Juliet C. Beavis ◽  
Judith Greenwood ◽  
Cornelia Gewert ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Enterotoxigenic Escherichia Coli ◽  
Gene Encoding ◽  
Double Blind ◽  
Content Type ◽  
Double Blind Placebo ◽  
Heat Stable ◽  
Heat Labile ◽  
Colonization Factors ◽  
Viable Approach

ABSTRACTLive attenuated oral enterotoxigenicEscherichia coli(ETEC) vaccines have been demonstrated to be safe and immunogenic in human volunteers and to provide a viable approach to provide protection against this important pathogen. This report describes the construction of new ETEC vaccine candidate strains from recent clinical isolates and their characterization. All known genes for ETEC toxins were removed, and attenuating deletion mutations were made in thearoC,ompC, andompFchromosomal genes. An isolate expressing coli surface antigen 2 (CS2), CS3, heat-labile toxin (LT), heat-stable toxin (ST), and enteroaggregativeEscherichia coliheat-stable toxin 1 (EAST1) was attenuated to generate ACAM2007. The subsequent insertion of the operon encoding CS1 created ACAM2017, and this was further modified by the addition of an expression cassette containing theeltBgene, encoding a pentamer of B subunits of LT (LTB), to generate ACAM2027. Another isolate expressing CS5, CS6, LT, ST, and EAST1 was attenuated to generate ACAM2006, from which a lysogenic prophage was deleted to create ACAM2012 and an LTB gene was introduced to form ACAM2022. Finally, a previously described vaccine strain, ACAM2010, had theeltBgene incorporated to generate ACAM2025. All recombinant genes were incorporated into the chromosomal sites of the attenuating mutations to ensure maximal genetic stability. The expression of the recombinant antigens and the changes in plasmids accompanying the deletion of toxin genes are described. Strains ACAM2025, ACAM2022, and ACAM2027 have been combined to create the ETEC vaccine formulation ACE527, which has recently successfully completed a randomized, double-blind, placebo-controlled phase I trial and is currently undergoing a randomized, double-blind placebo-controlled phase II challenge trial, both in healthy adult volunteers.

scholarly journals Genotypic characterization of Egypt enterotoxigenic Escherichia coli isolates expressing coli surface antigen 6

2013 ◽  
Vol 7 (02) ◽  
pp. 090-100 ◽  
Author(s):  
Atef M El-Gendy ◽  
Adel Mansour ◽  
Hind I Shaheen ◽  
Marshall R Monteville ◽  
Adam W Armstrong ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Surface Antigen ◽  
Protective Immunity ◽  
Surface Antigens ◽  
Enterotoxigenic Escherichia Coli ◽  
Mechanisms Of Resistance ◽  
E Coli ◽  
Colonization Factor ◽  
Factor Expression

Introduction: One approach to control enterotoxigenic Escherichia coli (ETEC) infections has been to develop vaccines focused on inducing protective immunity against surface expressed antigenic factors. One such factor is coli surface antigen 6 (CS6); ETEC isolates expressing CS6 may also simultaneously co-express surface antigens CS4 or CS5. However, there is little information regarding the inter-relationships of isolates expressing the CS6 antigen alone or in combination with CS4 or CS5. Methodology: A total of 62 CS6-associated ETEC isolates were evaluated for their antimicrobial susceptibility, mechanisms of resistance, toxin genes, colonization factor expression, and XbaI-pulsed-field gel electrophoretic profiles. Results: We observed 46 XbaI profiles; 31 were exclusive to ETEC expressing CS6 alone and 15 among the ETEC co-expressing CS4 or CS5. Nearly half (47%) of these isolates were resistant to ampicillin, a third (37%) of the isolates were resistant to trimethoprim-sulfamethoxazole, and 24% of the isolates were tetracycline-resistant. A blaTEM gene was detected in 24 (83%) ampicillin-resistant isolates. Trimethoprim-sulfamethoxazole-resistant isolates (n = 23) carried either sulI (n = 1, 4%), sulII (n = 8, 35%) or both genes (n = 10, 43%); 4 had no detectable sul gene. Conclusions: Our results show a lack of clonality among Egypt CS6 E. coli isolates and supports the use and the further research on vaccines targeting this cell surface antigen.

scholarly journals Disease Burden Due to Enterotoxigenic Escherichia coli in the First 2 Years of Life in an Urban Community in Bangladesh

2007 ◽  
Vol 75 (8) ◽  
pp. 3961-3968 ◽  
Author(s):  
Firdausi Qadri ◽  
Amit Saha ◽  
Tanvir Ahmed ◽  
Abdullah Al Tarique ◽  
Yasmin Ara Begum ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Incidence Rates ◽  
Enterotoxigenic Escherichia Coli ◽  
Healthy Children ◽  
Heat Stable ◽  
Colonization Factors ◽  
Asymptomatic Infections ◽  
Rotavirus Diarrhea ◽  
Diarrheal Morbidity

ABSTRACT A cohort of 321 children was followed from birth up to 2 years of age to determine the incidence of enterotoxigenic Escherichia coli (ETEC) in Bangladesh. The average number of diarrheal days and incidence rates were 6.6 and 2.3/child/year, respectively. ETEC was the most common pathogen and was isolated in 19.5% cases, with an incidence of 0.5 episode/child/year. The prevalence of rotavirus diarrhea was lower (10%). ETEC expressing the heat-stable enterotoxin (ST) was predominant. Strains isolated from diarrheal cases were positive for colonization factors (CFs) in higher frequency (66%) than from healthy children (33%) (P < 0.001). The heat-labile toxin (LT)-positive strains from healthy children were more often CF negative (92%) than those isolated from children with diarrhea (73%) (P < 0.001). In children with symptomatic or asymptomatic infections by CFA/I, CS1 plus CS3, CS2 plus CS3, or CS5 plus CS6 strains, a repeat episode of diarrhea or infection by the homologous CF type was uncommon. Repeat symptomatic infections were noted mostly for LT- and ST-expressing ETEC. ETEC diarrhea was more prevalent in children in the A and AB groups than in those in the O blood group (P = 0.032 to 0.023). Children with ETEC diarrhea were underweight and growth stunted at the 2-year follow-up period, showing the importance of strategies to prevent and decrease ETEC diarrheal morbidity in children.

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