المؤلفون: Sheikh, Alaullah, Tumala, Brunda, Vickers, Tim J, Martin, John C, Rosa, Bruce A, Sabui, Subrata, Basu, Supratim, Simoes, Rita D, Mitreva, Makedonka, Storer, Chad, Tyksen, Erik, Head, Richard D, Beatty, Wandy, Said, Hamid M, Fleckenstein, James M

المصدر: Nature Communications. 13(1)

مصطلحات موضوعية: Microbiology, Biological Sciences, Biomedical and Clinical Sciences, Clinical Sciences, Infectious Diseases, Vaccine Related, Prevention, Nutrition, Foodborne Illness, Emerging Infectious Diseases, Biodefense, Rare Diseases, Pediatric, Biotechnology, Genetics, Digestive Diseases, Aetiology, 2.1 Biological and endogenous factors, Zero Hunger, Mice, Animals, Enterotoxins, Escherichia coli Proteins, Enterotoxigenic Escherichia coli, Escherichia coli Infections, Diarrhea, Malnutrition

الوصف: Enterotoxigenic E. coli (ETEC) produce heat-labile (LT) and/or heat-stable (ST) enterotoxins, and commonly cause diarrhea in resource-poor regions. ETEC have been linked repeatedly to sequelae in children including enteropathy, malnutrition, and growth impairment. Although cellular actions of ETEC enterotoxins leading to diarrhea are well-established, their contributions to sequelae remain unclear. LT increases cellular cAMP to activate protein kinase A (PKA) that phosphorylates ion channels driving intestinal export of salt and water resulting in diarrhea. As PKA also modulates transcription of many genes, we interrogated transcriptional profiles of LT-treated intestinal epithelia. Here we show that LT significantly alters intestinal epithelial gene expression directing biogenesis of the brush border, the major site for nutrient absorption, suppresses transcription factors HNF4 and SMAD4 critical to enterocyte differentiation, and profoundly disrupts microvillus architecture and essential nutrient transport. In addition, ETEC-challenged neonatal mice exhibit substantial brush border derangement that is prevented by maternal vaccination with LT. Finally, mice repeatedly challenged with toxigenic ETEC exhibit impaired growth recapitulating the multiplicative impact of recurring ETEC infections in children. These findings highlight impacts of ETEC enterotoxins beyond acute diarrheal illness and may inform approaches to prevent major sequelae of these common infections including malnutrition that impact millions of children.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2pm09648Test

المؤلفون: Dong Wang, Yanjun He, Kexin Liu, Shouxiang Deng, Yuying Fan, Yun Liu

المصدر: Frontiers in Microbiology, Vol 13 (2022)

مصطلحات موضوعية: sodium humate, mice, enterotoxigenic Escherichia coli K88, intestinal barrier integrity, intestinal microbiota, metabolome, Microbiology, QR1-502

الوصف: Enterotoxigenic Escherichia coli (ETEC) can damage intestinal epithelial barrier function and lead to serious intestinal diarrhea in newborns and young animals. Sodium humate (HNa) is natural organic bioactive compound possessing antibacterial, anti-inflammatory, and anti-diarrheal properties. This study investigated the alleviative potential of HNa on the impaired intestinal barrier and intestinal inflammation, and regulatory effects on gut microbiota and metabolites in ETEC K88 infected mice. A total of 30 female mice were randomly assigned into three groups. The mice in the control and ETEC groups were gavaged with 0.2 mL of sterile saline, while the mice in the ETEC + HNa group were gavaged with 0.2 mL of 5% HNa, daily. On day 8, the mice in ETEC and ETEC + HNa group were challenged with ETEC K88. The trial lasted for 12 days. HNa administration elevated ETEC K88-induced body weight loss and ameliorated jejunum and colon pathological injury. HNa also reduced the levels of pro-inflammatory cytokines in the serum, jejunum, and colon. Additionally, HNa reduced intestinal barrier damage by up-regulating the expression of tight junction proteins (TJPs) and mucosal repair factors. 16s rDNA gene sequencing results showed that HNa increased the abundance of beneficial bacteria Lactobacillus, Prevotella_9, and Odoribacter but decreased the abundance of pathogenic bacteria Escherichia and Gastranaerophilales in the feces of mice. Moreover, metabolomic analysis revealed that the concentrations of 15 metabolites, the pathways of protein digestion and absorption, and propanoic acid metabolism were changed by HNa administration. In conclusion, HNa could alleviate ETEC K88-induced intestinal dysfunction through restoring intestinal barrier integrity, modulating gut microbiota, and metabolites.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmicb.2022.809086/fullTest; https://doaj.org/toc/1664-302XTest

الوصول الحر: https://doaj.org/article/26e47df54bf14081b05bb1763f941b4aTest

المؤلفون: Haihua Li, Zhiyuan Shang, Xuejiao Liu, Yingying Qiao, Kewei Wang, Jiayun Qiao

المصدر: Frontiers in Immunology, Vol 12 (2021)

مصطلحات موضوعية: Clostridium butyricum, enterotoxigenic Escherichia coli K88, oxidative damage, p62-Keap1-Nrf2 signaling pathway, cecal microbiota, mice, Immunologic diseases. Allergy, RC581-607

الوصف: Clostridium butyricum (CB) can enhance antioxidant capacity and alleviate oxidative damage, but the molecular mechanism by which this occurs remains unclear. This study used enterotoxigenic Escherichia coli (ETEC) K88 as a pathogenic model, and the p62-Keap1-Nrf2 signaling pathway and intestinal microbiota as the starting point to explore the mechanism through which CB alleviates oxidative damage. After pretreatment with CB for 15 d, mice were challenged with ETEC K88 for 24 h. The results suggest that CB pretreatment can dramatically reduce crypt depth (CD) and significantly increase villus height (VH) and VH/CD in the jejunum of ETEC K88-infected mice and relieve morphological lesions of the liver and jejunum. Additionally, compared with ETEC-infected group, pretreatment with 4.4×106 CFU/mL CB can significantly reduce malondialdehyde (MDA) level and dramatically increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels in the serum. This pretreatment can also greatly increase the mRNA expression levels of tight junction proteins and genes related to the p62-Keap1-Nrf2 signaling pathway in the liver and jejunum in ETEC K88-infected mice. Meanwhile, 16S rDNA amplicon sequencing revealed that Clostridium disporicum was significantly enriched after ETEC K88 challenge relative to the control group, while Lactobacillus was significantly enriched after 4.4×106 CFU/mL CB treatment. Furthermore, 4.4×106 CFU/mL CB pretreatment increased the short-chain fatty acid (SCFA) contents in the cecum of ETEC K88-infected mice. Moreover, we found that Lachnoclostridium, Roseburia, Lactobacillus, Terrisporobacter, Akkermansia, and Bacteroides are closely related to SCFA contents and oxidative indicators. Taken together, 4.4×106 CFU/mL CB pretreatment can alleviate ETEC K88-induced oxidative damage through activating the p62-Keap1-Nrf2 signaling pathway and remodeling the cecal microbiota community in mice.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2021.771826/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/334a4e31904f44fc80289c713d1b9c6bTest

المؤلفون: Medeiros, P.H.Q.S., Bolick, D.T., Barry, E.M.

مصطلحات موضوعية: preclinical research, Bacterial Infections, Shigella flexneri, Enterotoxigenic Escherichia coli, Vaccines, Mice

الوصف: Vaccine studies for Shigella flexneri and enterotoxigenic Escherichia coli have been impaired by the lack of optimal animal models. We used two murine models to show that a S. flexneri 2a bivalent vaccine (CVD 1208S-122) expressing enterotoxigenic Escherichia coli colonization factor antigen-I (CFA/I) and the binding subunits A2 and B of heat labile-enterotoxin (LTb) is immunogenic and protects against weight loss and diarrhea. These findings document the immunogenicity and pre-clinical efficacy effects of CVD 1208S-122 vaccine and suggest that further work can help elucidate relevant immune responses and ultimately its clinical efficacy in humans. Copyright 2020, The Author(s). ; This work was supported by National Institutes of Health (NIH) under NIH Award Number U19 AI109776 (CETR, Centers for Excellence for Translational Research, PI Myron Levine) from the National Institute of Allergy and Infectious Diseases (NIAID); and by Bill & Melinda Gates Foundation under Opportunity ID OPP1137923 (Host, pathogen and pathogen interaction determinants of environmental enteric dysfunction). National Institutes of Health, NIH: U19 AI109776 Israeli Centers for Research Excellence, I-CORE ; https://doi.org/10.1038/s41541-020-0180-yTest

العلاقة: npj Vaccines; https://www.scopus.com/inward/record.uri?eid=2-s2.0-85082751265&doi=10.1038%2fs41541-020-0180-y&partnerID=40&md5=7a53678d7e4654fc0dd7f859c9ad2e00Test; http://hdl.handle.net/10713/12537Test

الإتاحة: https://doi.org/10.1038/s41541-020-0180-yTest
http://hdl.handle.net/10713/12537Test

المؤلفون: Xiuliang Ding, Haitao Yu, Shiyan Qiao

المصدر: International Journal of Molecular Sciences; Volume 21; Issue 18; Pages: 6500

مصطلحات موضوعية: enterotoxigenic Escherichia coli, microcin J25, intestinal epithelial barrier, intestinal inflammation, mice, pathogen, mitogen-activated protein kinase, nuclear factor κB

جغرافية الموضوع: agris

الوصف: Bacterial resistance leads to severe public health and safety issues worldwide. Alternatives to antibiotics are currently needed. A promising lasso peptide, microcin J25 (MccJ25), is considered to be the best potential substitute for antibiotics to treat pathogen infection, including enterotoxigenic Escherichia coli (ETEC). This study evaluated the efficacy of MccJ25 in the prevention of ETEC infection. Forty-five female BALB/c mice of clean grade (aged seven weeks, approximately 16.15 g) were randomly divided into three experimental groups as follows: (i) control group (uninfected); (ii) ETEC infection group; (iii) MccJ25 + ETEC group. Fifteen mice per group in five cages, three mice/cage. MccJ25 conferred effective protection against ETEC-induced body weight loss, decrease in rectal temperature and increase in diarrhea scores in mice. Moreover, in ETEC-challenged mice model, MccJ25 significantly improved intestinal morphology, decreased intestinal histopathological scores and attenuated intestinal inflammation by decreasing proinflammatory cytokines and intestinal permeability, including reducing serum diamine oxidase and D-lactate levels. MccJ25 enhanced epithelial barrier function by increasing occludin expression in the colon and claudin-1 expression in the jejunum, ultimately improving intestinal health of host. MccJ25 was further found to alleviate gut inflammatory responses by decreasing inflammatory cytokine production and expression via the activation of the mitogen-activated protein kinase and nuclear factor κB signaling pathways. Taken together, the results indicated that MccJ25 protects against ETEC-induced intestinal injury and intestinal inflammatory responses, suggesting the potential application of MccJ25 as an excellent antimicrobial or anti-inflammation agent against pathogen infections.

وصف الملف: application/pdf

العلاقة: Molecular Pathology, Diagnostics, and Therapeutics; https://dx.doi.org/10.3390/ijms21186500Test

الإتاحة: https://doi.org/10.3390/ijms21186500Test

المؤلفون: Poole, S.T., Maciel, Jr., M., Dinadayala, Premkumar

مصطلحات موضوعية: CS6, Enterotoxigenic Escherichia coli, Mice, Vaccines

الوصف: CS6, a prevalent surface antigen expressed in nearly 20% of clinical enterotoxigenic Escherichia coli (ETEC) isolates, is comprised of two major subunit proteins, CssA and CssB. Using donor strand complementation, we constructed a panel of recombinant proteins of 1 to 3 subunits that contained combinations of CssA and/or CssB subunits and a donor strand, a C-terminal extension of 16 amino acids that was derived from the N terminus of either CssA or CssB. While the entire panel of recombinant proteins could be obtained as soluble, folded proteins, it was observed that the proteins possessing a heterologous donor strand, derived from the CS6 subunit different from the C-terminal subunit, had the highest degree of physical and thermal stability. Immunological characterization of the proteins, using a murine model, demonstrated that robust anti-CS6 immune responses were generated from fusions containing both CssA and CssB. Proteins containing only CssA were weakly immunogenic. Heterodimers, i.e., CssBA and CssAB, were sufficient to recapitulate the anti-CS6 immune response elicited by immunization with CS6, including the generation of functional neutralizing antibodies, as no further enhancement of the response was obtained with the addition of a third CS6 subunit. Our findings here demonstrate the feasibility of including a recombinant CS6 subunit protein in a subunit vaccine strategy against ETEC. Copyright 2019 American Society for Microbiology. All Rights Reserved. ; We thank the Walter Reed Army Institute of Research for the provision of recombinant CS6. Additionally, we are thankful for the technical support from Glomil Corbin, William Hulsey, Diana Zhang, Patrick Bonifassi, and Laurence Fourrichon. We also acknowledge Julianne Rollenhagen for her assistance in reviewing the manuscript and Claudia Costabile for her assistance with image formatting. This research was supported by U.S. Army Military Infectious Diseases Research Program Work Unit no. U.S. Navy 6000.RAD1.DA2.A0307, the Henry M. Jackson Foundation ...

العلاقة: Infection and Immunity; https://www.scopus.com/inward/record.uri?eid=2-s2.0-85061984026&doi=10.1128%2fIAI.00788-18&partnerID=40&md5=17f88f1f330b974d0712ec8897eee7a9Test; http://hdl.handle.net/10713/8673Test

الإتاحة: https://doi.org/10.1128/IAI.00788-18Test
http://hdl.handle.net/10713/8673Test

المؤلفون: Ali Akgul, Massimo Maddaloni, David W. Pascual, Carol Hoffman, Andrew S. Nelson, Ella Bhagyaraj

المصدر: Immunol Lett

مصطلحات موضوعية: Blood Glucose, CD4-Positive T-Lymphocytes, Primary Cell Culture, Immunology, Fimbria, Administration, Oral, Mice, Transgenic, Spleen, Biology, medicine.disease_cause, Article, Mice, Antigen, Transforming Growth Factor beta, Enterotoxigenic Escherichia coli, Bystander effect, medicine, Animals, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase, Immunology and Allergy, Indoleamine 2,3-dioxygenase, Cells, Cultured, NOD mice, Antigens, Bacterial, Probiotics, Dendritic Cells, Coculture Techniques, Lactococcus lactis, Bacterial adhesin, Disease Models, Animal, Diabetes Mellitus, Type 1, medicine.anatomical_structure, Female, Fimbriae Proteins, Lymph Nodes

الوصف: Colonization factor antigen I (CFA/I) fimbria, an adhesin from enterotoxigenic Escherichia coli, confers protection in murine autoimmune models for type 1 diabetes (T1D), multiple sclerosis, and rheumatoid arthritis. Although CFA/I fimbriae's initial mode of action is in a bystander or in an antigen (Ag)-independent fashion, protection is ultimately dependent upon the induction and/or activation of auto-Ag-specific regulatory T cells (Tregs). However, little is known about how protection transitions from bystander suppression to Ag-specific Tregs. Since dendritic cells (DCs) play an integral role in fate decisions for T cells becoming inflammatory or tolerogenic, the described study tests the hypothesis that Lactococcus lactis expressing CFA/I (LL-CFA/I) stimulates DCs to establish a regulatory microenvironment. To this end, bone marrow-derived dendritic cells (BMDCs) were infected in vitro with LL-CFA/I. Results revealed increased production of IL-10, TGF-β, and indoleamine 2,3-deoxygenase (IDO). Although co-culture of LL-CFA/I infected BMDCs with naive T cells did not promote Foxp3 expression, TNF-α and IFN-γ production was suppressed. NOD mice orally dosed with LL-CFA/I showed an increase in regulatory plasmacytoid DCs (pDCs) expressing IDO and TGF-β in pancreatic lymph nodes (PaLNs) and spleen three days post-treatment. However, Tregs did not appear in the mucosal inductive sites until much later. These findings show that LL-CFA/I influences specific DC populations to establish tolerance.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0299421e3af10d90364d5c97d708dfb6Test
https://doi.org/10.1016/j.imlet.2021.07.009Test

المؤلفون: Hongmei Jiang, Naiyuan Liu, Jun Fang, Gang Liu, Lingsi Zhou

المصدر: Mediators of Inflammation, Vol 2021 (2021)
Mediators of Inflammation

مصطلحات موضوعية: Diarrhea, Male, Article Subject, Colon, Firmicutes, Immunology, Crypt, Prevotellaceae, Gut flora, medicine.disease_cause, digestive system, Microbiology, Proinflammatory cytokine, Mice, Enterotoxigenic Escherichia coli, Pathology, medicine, Animals, RB1-214, Inflammation, biology, Lachnospiraceae, Cell Biology, biology.organism_classification, Flavobacteriaceae, Gastrointestinal Microbiome, Jejunum, Cytokines, Oligopeptides, Research Article

الوصف: Background/Aims. Changing gut microbiota is one of the most common causes of host gut inflammation. The active triple peptides, lle-Gln-Trp (IQW) and lle-Arg-Trp (IRW), cause remarkable changes to gut microbiota. The effects of the triple peptides IQW and IRW in gut-damage treatment were explored in this study via an enterotoxigenic Escherichia coli- (ETEC-) induced mouse model. Methods. The mice were randomly distributed into four groups: (a) control (CTRL) group, (b) ETEC group, (c) IQW-ETEC group, and (d) IRW-ETEC group. Villus length and crypt depth were measured after hematoxylin and eosin staining. The inflammatory reaction was analyzed via inflammatory cytokines (i.e., TNF-α, IL-1β, IL-6, and IL-10) using the enzyme-linked immunosorbent assay (ELISA). The microbiota in the colon was sequenced using 16S ribosomal RNA. Results. The villus length decreased, the crypt depth decreased, and the expression of inflammatory cytokines (i.e., TNF-α, IL-1β, IL-6, and IL-10) increased due to ETEC. In the IRW-ETEC and IQW-ETEC groups, the Shannon index decreased ( P < 0.05 ). IQW and IRW increased the abundance of Firmicutes, Proteobacteria, Clostridiales, Lachnospiraceae, and Alloprevotella; contrastingly, it decreased the abundance of Epsilonproteobacteria, Erysipelotrichales, Prevotellaceae, and Flavobacteriaceae compared to the ETEC group (P

وصف الملف: text/xhtml

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7a0886b139e62199927ebbf2389c8cbaTest
https://doi.org/10.1155/2021/2752265Test

المؤلفون: Hyesuk Seo, Qiangde Duan, Ipshita Upadhyay, Weiping Zhang

المصدر: Appl Environ Microbiol

مصطلحات موضوعية: Diarrhea, Travel, Ecology, Public and Environmental Health Microbiology, Escherichia coli Proteins, Bacterial Toxins, Applied Microbiology and Biotechnology, Antibodies, Bacterial, Disease Models, Animal, Enterotoxins, Mice, Immunoglobulin G, Animals, Enterotoxigenic Escherichia coli, Humans, Vaccines, Combined, Adhesins, Bacterial, Child, Escherichia coli Infections, Food Science, Biotechnology

الوصف: There are no licensed vaccines against enterotoxigenic Escherichia coli (ETEC), a leading cause of children’s diarrhea and travelers’ diarrhea. Recently, protein-based vaccine candidate MecVax was demonstrated to induce functional antibodies against both ETEC toxins (heat-stable toxin [STa] and heat-labile toxin [LT]) and seven ETEC adhesins (CFA/I and CS1 to CS6) and to protect against ETEC clinical diarrhea or intestinal colonization preclinically. Those studies used intraperitoneal, intramuscular, and intradermal routes, and a dose range for MecVax protein antigens, toxoid fusion 3xSTa(N12S)-mnLT(R192G/L211A), and adhesin CFA/I/II/IV MEFA has not been investigated. Here, we further characterized MecVax broad immunogenicity, utilizing a subcutaneous route, and examined vaccine dose-dependent antibody response effects and also antibody functional activities against ETEC enterotoxicity and bacterial adherence. Data showed that mice immunized subcutaneously with MecVax developed robust IgG responses to seven ETEC adhesins (CFA/I, as well as CS1 to CS6) and two toxins (STa and LT). At a subcutaneous dose of 25, 20, or 10 μg or at an intramuscular dose of 12, 6, or 3 μg, MecVax induced similar levels IgG responses to the targeted toxins and adhesins, and these antibodies exhibited equivalent functional activities against ETEC toxin enterotoxicity and bacterial adherence. Once the intramuscular dose was decreased to 1 μg, vaccine-induced antibodies were significantly reduced and no longer neutralized STa enterotoxicity. The results indicated that MecVax administered subcutaneously is broadly immunogenic and, at an intramuscular dose of 3 μg, can induce functional antitoxin and anti-adhesin antibodies in mice, providing instructive information for future vaccine dose studies in humans and accelerating MecVax vaccine development. IMPORTANCE Enterotoxigenic Escherichia coli (ETEC) is a leading cause of children’s diarrhea and the most common cause of travelers’ diarrhea. ETEC infections are responsible for >200 million diarrhea clinical cases and near 100,000 deaths annually. Currently, there are no licensed vaccines for ETEC diarrhea. The protein-based vaccine candidate MecVax unprecedentedly targets two ETEC toxins (STa and LT, produced by all ETEC strains) and seven ETEC adhesins (CFA/I, as well as CS1 to CS6, associated with >60% of ETEC clinical diarrhea cases) and has been demonstrated to be broadly immunogenic and cross protective; as such, it represents a potentially effective multivalent vaccine against ETEC-associated children’s and travelers’ diarrhea. This study further confirmed MecVax broad immunogenicity and evaluated the vaccine antigen dose effect on the induction of antigen-specific antibody responses in mice and on antibody functional activities against ETEC toxin enterotoxicity and bacterial adherence, yielding useful information for future human volunteer studies and the development of MecVax as an effective ETEC vaccine.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ade1e6756040cf1f61ba2b14ea790458Test
https://europepmc.org/articles/PMC9469710Test/

المؤلفون: Di Zhang, Longfei Yang, Weiheng Su, Yuan Zhao, Xin Ma, Haizhu Zhou, Bo Xu, Kaiqi Zhang, Hongxia Ma

المصدر: Frontiers in Microbiology, Vol 8 (2018)

مصطلحات موضوعية: aquaporin-4, diarrhea, enterotoxigenic Escherichia coli, ileum, mice, Microbiology, QR1-502

الوصف: Enterotoxigenic Escherichia coli (ETEC) are opportunistic pathogens that colonize the small intestine, produce enterotoxins and induce diarrhea. Some aquaporins (AQPs), such as AQP3 and AQP8, have been reported to participate in diarrhea by decreasing cellular influx in the gastrointestinal (GI) tract. AQP4 is another important water channel in the GI tract, but its role in ETEC-induced diarrhea has not been reported. Here, we demonstrated the potential roles of AQP4 in ETEC-induced diarrhea. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting showed that AQP4 was expressed in the mouse ileum, but not in the duodenum or jejunum while immunohistochemical staining showed that AQP4 localized to the basolateral membrane of ileum epithelial cells. Using an ETEC-induced mice diarrhea model, we demonstrated that both AQP4 mRNA level and the AQP4 protein level in the ileum decreased gradually over a time course of 7 days. These results suggest that AQP4 plays a role in the pathogenesis of ETEC-induced diarrhea by mediating water transport.

وصف الملف: electronic resource

العلاقة: http://journal.frontiersin.org/article/10.3389/fmicb.2017.02655/fullTest; https://doaj.org/toc/1664-302XTest

الوصول الحر: https://doaj.org/article/7f5bb18bc3c04946a24abd1b568c4ee6Test