Proportions of IgA antibodies targeting glycosylated epitopes of secreted Escherichia coli mucinase YghJ in initial plasmablast response differ from salivary and intestinally secreted IgA.

Mucosal infections normally cause an immune response including activation of antigen-specific B cells in regional mucosa-associated lymphoid tissue. After recirculation of plasmablasts, and maturation at mucosal surfaces or bone marrow, plasma cells produce secretory or systemic IgA. It remains uncertain to what extent secretory and systemic IgA share the same target specificities.

Inflammation, the kynurenines, and mucosal injury during human experimental enterotoxigenic Escherichia coli infection.

Enterotoxigenic Escherichia coli (ETEC) is an important cause of diarrhea in children and travelers, especially in low- and middle-income countries. ETEC is a non-invasive gut pathogen colonizing the small intestinal wall before secreting diarrhea-inducing enterotoxins. We sought to investigate the impact of ETEC infection on local and systemic host defenses by examining plasma markers of inflammation and mucosal injury as well as kynurenine pathway metabolites.

Colicins and T6SS-based competition systems enhance enterotoxigenic (ETEC) competitiveness.

Diarrheal diseases are still a significant problem for humankind, causing approximately half a million deaths annually. To cause diarrhea, enteric bacterial pathogens must first colonize the gut, which is a niche occupied by the normal bacterial microbiota. Therefore, the ability of pathogenic bacteria to inhibit the growth of other bacteria can facilitate the colonization process.

Reduced Plasma Guanylin Levels Following Enterotoxigenic -Induced Diarrhea.

The intestinal peptide hormones guanylin (GN) and uroguanylin (UGN) interact with the epithelial cell receptor guanylate cyclase C to regulate fluid homeostasis. Some enterotoxigenic (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.

Dynamics of circulating lymphocytes responding to human experimental enterotoxigenic Escherichia coli infection.

Enterotoxigenic Escherichia coli (ETEC) is an important cause of children's and travelers' diarrhea, with no licensed vaccine. This study aimed to explore the role of cellular immunity in protection against human ETEC infection. Nine volunteers were experimentally infected with ETEC, of which six developed diarrhea.

Strong Association between Diarrhea and Concentration of Enterotoxigenic Strain TW10722 in Stools of Experimentally Infected Volunteers.

Enterotoxigenic (ETEC) strains are a major cause of diarrheal illness in children and travelers in low- and middle-income countries. When volunteers are infected with ETEC strains, as part of experimental infection studies, some do not develop diarrhea. To improve our understanding of how these volunteers are protected, we investigated the association between stool ETEC DNA concentration, as determined by quantitative PCR, and the development and severity of disease in 21 volunteers who had been experimentally infected with ETEC strain TW10722.

Umbilical Cord Stump Infections in Central Uganda: Incidence, Bacteriological Profile, and Risk Factors.

Umbilical cord stump infection (omphalitis) is a risk factor for neonatal sepsis and death. We assessed the incidence of omphalitis, described the bacteriological and antibiotic-resistance profile of potentially pathogenic bacteria isolated from the umbilical cord stump of omphalitis cases, and evaluated whether bacteria present in the birth canal during birth predicted omphalitis. We enrolled 769 neonates at birth at three primary healthcare facilities and followed them for 28 days with scheduled visits on days 3, 7, 14, and 28.

Characterization of Glycosylation-Specific Systemic and Mucosal IgA Antibody Responses to Mucinase YghJ (SslE).

Efforts to develop broadly protective vaccines against pathogenic are ongoing. A potential antigen candidate for vaccine development is the metalloprotease YghJ, or SslE. YghJ is a conserved mucinase that is immunogenic, heavily glycosylated, and produced by most pathogenic .

Vaginal colonization with antimicrobial-resistant bacteria among women in labor in central Uganda: prevalence and associated factors.

Background: According to WHO ( CISMAC. Centre for Intervention Science in Maternal and Child health), the antimicrobial resistant bacteria considered to be clinically most important for human health and earmarked for surveillance include extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, carbapenem-resistant bacteria, methicillin-resistant (MRSA) and, macrolide-lincosamide-streptogramin B -resistant vancomycin-resistant (VRSA) Staphylococcus aureus and vancomycin-resistant Enterococcus (VRE). If these bacteria are carried in the female genital tract, they may be transmitted to the neonate causing local or systemic neonatal infections that can be difficult to treat with conventionally available antimicrobials.

Distinct Metabolic Features of Pathogenic Escherichia coli and Shigella spp. Determined by Label-Free Quantitative Proteomics.

Escherichia coli and Shigella spp. causing illnesses in humans represent a genotypically and phenotypically diverse group of pathogens. Although E.

Human Mucosal IgA Immune Responses against Enterotoxigenic .

Infection with enterotoxigenic (ETEC) is a major contributor to diarrheal illness in children in low- and middle-income countries and travelers to these areas. There is an ongoing effort to develop vaccines against ETEC, and the most reliable immune correlate of protection against ETEC is considered to be the small intestinal secretory IgA response that targets ETEC-specific virulence factors. Since isolating IgA from small intestinal mucosa is technically and ethically challenging, requiring the use of invasive medical procedures, several other indirect methods are used as a proxy for gauging the small intestinal IgA responses.

Vaginal colonisation of women in labour with potentially pathogenic bacteria: a cross sectional study at three primary health care facilities in Central Uganda.

Background: Potentially pathogenic bacteria that colonise the lower genital tract of women in labour can be passed to the baby during birth. While many babies become colonised with these bacteria after delivery, a few develop neonatal infections. The lower genital tract is a reservoir for potential pathogens and a source of infection for neonates.

A new human challenge model for testing heat-stable toxin-based vaccine candidates for enterotoxigenic Escherichia coli diarrhea - dose optimization, clinical outcomes, and CD4+ T cell responses.

ClinicalTrials.gov ClinicalTrials.gov, Project ID: NCT02870751.

Experimental Infection of Human Volunteers with the Heat-Stable Enterotoxin-Producing Enterotoxigenic Strain TW11681.

Infection with enterotoxigenic (ETEC) producing the heat-stable enterotoxin (ST) is one of the most important causes of childhood diarrhoea in low- and middle-income countries. Here, we undertook a controlled human infection model (CHIM) study to investigate whether ST-producing ETEC strain TW11681 would be suitable for testing the protective efficacy of new ST-based vaccine candidates in vaccine challenge models. In groups of three, nine volunteers ingested 1 × 10, 1 × 10, or 1 × 10 colony-forming units (CFU) of TW11681.

Immunizations with Enterotoxigenic Escherichia coli Heat-Stable Toxin Conjugates Engender Toxin-Neutralizing Antibodies in Mice That Also Cross-React with Guanylin and Uroguanylin.

Infection with enterotoxigenic (ETEC) is a common cause of childhood diarrhea in low- and middle-income countries, as well as of diarrhea among travelers to these countries. In children, ETEC strains secreting the heat-stable toxin (ST) are the most pathogenic, and there are ongoing efforts to develop vaccines that target ST. One important challenge for ST vaccine development is to construct immunogens that do not elicit antibodies that cross-react with guanylin and uroguanylin, which are endogenous peptides involved in regulating the activity of the guanylate cyclase-C (GC-C) receptor.

Proliferation of enterotoxigenic strain TW11681 in stools of experimentally infected human volunteers.

Background: As part of the effort to develop an enterotoxigenic (ETEC) human challenge model for testing new heat-stable toxin (ST)-based vaccine candidates, a controlled human infection model study based on the ST-producing ETEC strain TW11681 was undertaken. Here, we estimate stool TW11681 DNA concentration and evaluate its association with dose, clinical symptoms, and with levels of antibodies targeting the CfaB subunit of the ETEC Colonization Factor Antigen I and the mucinase YghJ. Nine volunteers ingested different doses of the strain and were subsequently followed for 9 days with daily stool specimen collection and clinical examination.

Longitudinal cohort study of serum antibody responses towards Giardia lamblia variant-specific surface proteins in a non-endemic area.

Introduction/aims: The long-term humoral immune response after a natural giardiasis infection is not well understood. The aim of this study was to evaluate longitudinal serum IgA and IgG/M responses towards conserved regions of two Giardia variant-specific surface proteins (VSP) and whether these responses differ between Giardia assemblages and durations of infection.

Methods: We recruited thirty Giardia-positive patients, mainly returning travellers, and eighteen healthy adults presumed to be Giardia unexposed.

Comparative Proteomics of Enterotoxigenic Escherichia coli Reveals Differences in Surface Protein Production and Similarities in Metabolism.

Enterotoxigenic Escherichia coli (ETEC) infections are an important cause of diarrhea among young children living in low- and middle-income countries and visiting travelers. The development of effective vaccines is complicated by substantial genomic diversity that exists among ETEC isolates. To investigate how ETEC genomic variation is reflected at expressed proteome level, we applied label-free quantitative proteomics to seven human ETEC strains representing five epidemiologically important lineages.

An Evidenced-Based Scale of Disease Severity following Human Challenge with Enteroxigenic Escherichia coli.

Background: Experimental human challenge models have played a major role in enhancing our understanding of infectious diseases. Primary outcomes have typically utilized overly simplistic outcomes that fail to entirely account for complex illness syndromes. We sought to characterize clinical outcomes associated with experimental infection with enterotoxigenic Escherichia coli (ETEC) and to develop a disease score.

Improving genome annotation of enterotoxigenic Escherichia coli TW10598 by a label-free quantitative MS/MS approach.

The most commonly used genome annotation processes are to a great extent based on computational methods. However, those can only predict genes that have been described earlier or that have sequence signatures indicative of a gene function. Here, we report a synonymous proteogenomic approach for experimentally improving microbial genome annotation based on label-free quantitative MS/MS.

Experimental infection of healthy volunteers with enterotoxigenic Escherichia coli wild-type strain TW10598 in a hospital ward.

Background: Enterotoxigenic Escherichia coli (ETEC) is an important cause of childhood diarrhea in resource-limited regions. It is also an important cause of diarrhea in travellers to these areas.To evaluate the protective efficacy of new ETEC vaccines that are under development, there is a need to increase the capacity to undertake Phase IIB (human challenge) clinical trials and to develop suitable challenge models.

Case/control studies with follow-up: Constructing the source population to estimate effects of risk factors on development, disease, and survival.

If individuals in a case/control study are subsequently observed as a cohort of cases and a cohort of controls, weighted regression analyses can be used to estimate the association between the exposures initially recorded and events occurring during the follow-up of the 2 cohorts. Such analyses can be conceptualized as being undertaken on a reconstructed source population from which cases and controls stem. To simulate this population, the cohort of cases is added to the cohort of controls expanded with the reciprocal of the case disease incidence odds (the sampling weight) to include all individuals in the source population who did not develop the case disease.

Draft genome sequences of the diarrheagenic Escherichia coli collection.

We report the draft genome sequences of the collection referred to as the Escherichia coli DECA collection, which was assembled to contain representative isolates of the 15 most common diarrheagenic clones in humans (http://shigatox.net/new/). These genomes represent a valuable resource to the community of researchers who examine these enteric pathogens.

A comparative genomic analysis of diverse clonal types of enterotoxigenic Escherichia coli reveals pathovar-specific conservation.

Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrheal illness in children less than 5 years of age in low- and middle-income nations, whereas it is an emerging enteric pathogen in industrialized nations. Despite being an important cause of diarrhea, little is known about the genomic composition of ETEC. To address this, we sequenced the genomes of five ETEC isolates obtained from children in Guinea-Bissau with diarrhea.

Ancestral lineages of human enterotoxigenic Escherichia coli.

Enterotoxigenic Escherichia coli (ETEC) is a common cause of diarrhea among children living in and among travelers visiting developing countries. Human ETEC strains represent an epidemiologically and phenotypically diverse group of pathogens, and there is a need to identify natural groupings of these organisms that may help to explain this diversity. Here, we sought to identify most of the important human ETEC lineages that exist in the E.