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1دورية أكاديمية
المؤلفون: Jiangxu Yu, Jiyang Fu, Hongshuo Liu, Chao Kang, Zesong Wang, Yancheng Jin, Shuxuan Wu, Tianzhi Li, Ruicheng Yang, Meilin Jin, Huanchun Chen, Xiangru Wang
المصدر: Vaccines, Vol 12, Iss 3, p 304 (2024)
مصطلحات موضوعية: enterotoxigenic Escherichia coli (ETEC), lactic acid bacteria (LAB), oral vaccine, Medicine
الوصف: Enterotoxigenic Escherichia coli (ETEC) causes severe diarrhea in piglets. The current primary approach for ETEC prevention and control relies on antibiotics, as few effective vaccines are available. Consequently, an urgent clinical demand exists for developing an effective vaccine to combat this disease. Here, we utilized food-grade Lactococcus lactis NZ3900 and expression plasmid pNZ8149 as live vectors, together with the secreted expression peptide Usp45 and the cell wall non-covalent linking motif LysM, to effectively present the mutant LTA subunit, the LTB subunit of heat-labile enterotoxin, and the FaeG of F4 pilus on the surface of recombinant lactic acid bacteria (LAB). Combining three recombinant LAB as a live vector oral vaccine, we assessed its efficacy in preventing F4+ ETEC infection. The results demonstrate that oral immunization conferred effective protection against F4+ ETEC infection in mice and piglets lacking maternal antibodies during weaning. Sow immunization during late pregnancy generated significantly elevated antibodies in colostrum, which protected piglets against F4+ ETEC infection during lactation. Moreover, booster immunization on piglets during lactation significantly enhanced their resistance to F4+ ETEC infection during the weaning stage. This study highlights the efficacy of an oral LAB vaccine in preventing F4+ ETEC infection in piglets by combining the sow immunization and booster immunization of piglets, providing a promising vaccination strategy for future prevention and control of ETEC-induced diarrhea in piglets.
وصف الملف: electronic resource
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2دورية أكاديمية
المؤلفون: Da Qin, Ying Li, Xiaoyan Chen, Liyang Li, Guihua Wang, Xilin Hou, Liyun Yu
المصدر: Life, Vol 13, Iss 9, p 1936 (2023)
مصطلحات موضوعية: SIgA–ETEC F5 immune complex, enterotoxigenic Escherichia coli (ETEC), F5 fimbrial protein, secretory IgA, mucosal immune response, Science
الوصف: Although secretory IgA (SIgA) is the dominant antibody in mucosal secretions, the capacity of the SIgA–antigen complex to prime the activation of dendritic cells (DCs) and T cells in the intestinal epithelium is not well understood. To this end, the SIgA–ETEC F5 immune complexes (ICs) were prepared via Ni-NTA pull-down. After injecting the ICs into the intestines of SPF BALB/c mice, most ICs were observed in the Peyer’s patch (PP). We established a microfold (M) cell culture model in vitro for transport experiments and the inhibition test. To evaluate the priming effect of mucosal immunity, we employed the DC2.4 stimulation test, T lymphocyte proliferation assays, and cytokine detection assays. We found that the ICs were taken up via clathrin-dependent endocytosis through M cells. The high expression of costimulatory molecules CD86, CD80, and CD40 indicated that the ICs promoted the differentiation and maturation of DC2.4 cells. The stimulation index (SI) in the complex group was significantly higher than in the control group, suggesting that the ICs stimulated the proliferation of primed T cells. The secretion of some cytokines, namely TNF-α, IFN-γ, IL-2, IL-4, IL-5, and IL-6, in spleen cells from the immunized mice was upregulated. These results indicate that ETEC F5 delivery mediated by SIgA in PPs initiates mucosal immune responses.
وصف الملف: electronic resource
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3دورية أكاديمية
المصدر: Microorganisms, Vol 11, Iss 8, p 2088 (2023)
مصطلحات موضوعية: Enterotoxigenic Escherichia coli (ETEC), outer membrane vesicle (OMV), vaccine, immunogenicity, ultracentrifugation, ultrafiltration, Biology (General), QH301-705.5
الوصف: The study addresses Enterotoxigenic Escherichia coli (ETEC), a significant concern in low-income countries. Despite its prevalence, there is no licensed vaccine against ETEC. Bacterial vesicle-based vaccines are promising due to their safety and diverse virulence factors. However, cost-effective production requires enhancing vesicle yield while considering altered properties due to isolation methods. The proposed method involves heat treatment and ultrafiltration to recover vesicles from bacterial cultures. Two vesicle types, collected from heat-treated (HT-OMV) or untreated (NT-OMV) cultures, were compared. Vesicles were isolated via ultrafiltration alone (“complete”) or with ultracentrifugation (“sediment”). Preliminary findings suggest complete HT-OMV vesicles are suitable for an ETEC vaccine. They express important proteins (OmpA, OmpX, OmpW) and virulence factors (adhesin TibA). Sized optimally (50–200 nm) for mucosal vaccination, they activate macrophages, inducing marker expression (CD40, MHCII, CD80, CD86) and Th1/Th2 cytokine release (IL-6, MCP-1, TNF-α, IL12p70, IL-10). This study confirms non-toxicity in RAW 264.7 cells and the in vivo ability of complete HT-OMV to generate significant IgG2a/IgG1 serum antibodies. Results suggest promise for a cost-effective ETEC vaccine, requiring further research on in vivo toxicity, pathogen-specific antibody detection, and protective efficacy.
وصف الملف: electronic resource
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4دورية أكاديميةDeletion of FaeG alleviated Enterotoxigenic Escherichia coli F4ac-induced apoptosis in the intestine
المؤلفون: Pengpeng Xia, Yunping Wu, Siqi Lian, Guomei Quan, Yiting Wang, Guoqiang Zhu
المصدر: AMB Express, Vol 11, Iss 1, Pp 1-8 (2021)
مصطلحات موضوعية: Enterotoxigenic Escherichia coli (ETEC) F4ac, FaeG subunit, Apoptosis, Biotechnology, TP248.13-248.65, Microbiology, QR1-502
الوصف: Abstract Enterotoxigenic Escherichia coli (ETEC) F4ac is a major constraint to the development of the pig industry, which is causing newborn and post-weaning piglets diarrhea. Previous studies proved that FaeG is the major fimbrial subunit of F4ac E. coli and efficient for bacterial adherence and receptor recognition. Here we show that the faeG deletion attenuates both the clinical symptoms of F4ac infection and the F4ac-induced intestinal mucosal damage in piglets. Antibody microarray analysis and the detection of mRNA expression using porcine neonatal jejunal IPEC-J2 cells also determined that the absence of FaeG subunit alleviated the F4ac promoted apoptosis in the intestinal epithelial cells. Thus, targeted depletion of FaeG is still beneficial for the prevention or treatment of F4ac infection.
وصف الملف: electronic resource
العلاقة: https://doaj.org/toc/2191-0855Test
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5دورية أكاديمية
المؤلفون: Hyesuk Seo, Qiangde Duan, Weiping Zhang
المصدر: Gut Microbes, Vol 11, Iss 6, Pp 1486-1517 (2020)
مصطلحات موضوعية: enteric diseases, vaccinology, multiepitope fusion antigen (mefa), enterotoxigenic escherichia coli (etec), vibrio cholerae, shigella, nontyphoidal salmonella, campylobacter, rotavirus, norovirus, Diseases of the digestive system. Gastroenterology, RC799-869
الوصف: Enteric viral and bacterial infections continue to be a leading cause of mortality and morbidity in young children in low-income and middle-income countries, the elderly, and immunocompromised individuals. Vaccines are considered an effective and practical preventive approach against the predominantly fecal-to-oral transmitted gastroenteritis particularly in the resource-limited countries or regions where implementation of sanitation systems and supply of safe drinking water are not quickly achievable. While vaccines are available for a few enteric pathogens including rotavirus and cholera, there are no vaccines licensed for many other enteric viral and bacterial pathogens. Challenges in enteric vaccine development include immunological heterogeneity among pathogen strains or isolates, a lack of animal challenge models to evaluate vaccine candidacy, undefined host immune correlates to protection, and a low protective efficacy among young children in endemic regions. In this article, we briefly updated the progress and challenges in vaccines and vaccine development for the leading enteric viral and bacterial pathogens including rotavirus, human calicivirus, Shigella, enterotoxigenic Escherichia coli (ETEC), cholera, nontyphoidal Salmonella, and Campylobacter, and introduced a novel epitope- and structure-based vaccinology platform known as MEFA (multiepitope fusion antigen) and the application of MEFA for developing broadly protective multivalent vaccines against heterogenous pathogens.
وصف الملف: electronic resource
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6دورية أكاديمية
المصدر: Vaccines, Vol 10, Iss 12, p 2161 (2022)
مصطلحات موضوعية: live cholera vaccine, cold chain free, cholera toxin, heat-labile toxin, Vibrio cholerae O139, enterotoxigenic Escherichia coli (ETEC), Medicine
الوصف: In low- and middle-income countries, diarrhoeal diseases are the second most common cause of mortality in children, mainly caused by enterotoxin-producing bacteria, such as Shigella, Vibrio, Salmonella, and Escherichia coli. Cholera and traveller’s diarrhoea are caused by Vibrio cholerae (O1 and O139 serogroups) and enterotoxigenic Escherichia coli (ETEC), respectively. The cholera toxin (CT) produced by V. cholerae and the heat-labile enterotoxin (LT) of ETEC are closely related by structure, function, and the immunological response to them. There is no exclusive vaccine for ETEC; however, cholera vaccines based on the CT-B component elicit a short-term cross-protection against ETEC infection. In this context, the cross-protective efficacy of MyCholTM, a prototype cold-chain-free, live-attenuated, oral cholera vaccine against V. cholerae O139 was evaluated in BALB/c mice. The 100% lethal dose (LD100) of 109 CFU/mL of the ETEC H10407 strain was used for the challenge studies. The mice immunised with MyChol™ survived the challenge by producing anti-CT antibodies, which cross-neutralised the LT toxin with no body weight loss and no sign of diarrhoea. Compared to unimmunised mice, the immunised mice elicited the neutralising antitoxin that markedly decreased ETEC colonisation and fluid accumulation caused by ETEC H10407 in the intestines. The immunised mice recorded higher antibody titres, including anti-CT IgG, anti-LT IgG, anti-CT-B IgG, and anti-LTB IgG. Only a two-fold rise in anti-CT/CT-B/LT/LT-B IgA was recorded in serum samples from immunised mice. No bactericidal antibodies against ETEC H10407 were detected. This investigation demonstrates the safety, immunogenicity, and cross-protective efficacy of MyCholTM against the ETEC H10407 challenge in BALB/c mice.
وصف الملف: electronic resource
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7دورية أكاديمية
المؤلفون: Hyesuk Seo, Ti Lu, Sachin Mani, A. Louis Bourgeois, Richard Walker, David A. Sack, Weiping Zhang
المصدر: Human Vaccines & Immunotherapeutics, Vol 16, Iss 2, Pp 419-425 (2020)
مصطلحات موضوعية: dmlt, adjuvant, dose effect, cfa/i/ii/iv mefa, enterotoxigenic escherichia coli (etec), antibody response, Immunologic diseases. Allergy, RC581-607, Therapeutics. Pharmacology, RM1-950
الوصف: Double-mutant heat-labile toxin (dmLT, LTR192G/L211A) of enterotoxigenic Escherichia coli (ETEC) is an effective mucosal adjuvant. Recent studies have shown that dmLT also exhibits adjuvanticity for antigens administered parenterally. In this study, we subcutaneously (SC) immunized mice with the ETEC adhesin-based vaccine, CFA/I/II/IV MEFA (multiepitope fusion antigen), adjuvanted with dmLT and examined the impact of dmLT on antibody responses specific to the seven adhesins in the vaccine construction [CFA/I, CFA/II (CS1, CS2, CS3) and CFA/IV (CS4, CS5, CS6)]. Mice were immunized with a fixed dose of CFA/I/II/IV MEFA and ascending doses of dmLT adjuvant (0, 0.05, 0.1, 0.5 or 1.0 µg) to assess the potential dmLT dose response relationship. Data showed that dmLT enhanced systemic antibody responses to all seven antigens (CFA/I, CS1-CS6) targeted by MEFA in a dose-dependent way. The adjuvant effect of dmLT on the MEFA construct plateaued at a dose of 0.1 µg. Results also indicated that dmLT is an effective parenteral adjuvant when given by the SC route with the ETEC adhesin MEFA vaccine and that antibody enhancement was achieved with relatively low doses. These observations suggest the potential usefulness of dmLT for parenteral ETEC vaccine candidates and also perhaps for vaccines against other pathogens.
وصف الملف: electronic resource
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8دورية أكاديمية
المؤلفون: Chao Yang, Yinghui Li, Le Zuo, Min Jiang, Xianglilan Zhang, Li Xie, Miaomiao Luo, Yiying She, Lei Wang, Yixiang Jiang, Shuang Wu, Rui Cai, Xiaolu Shi, Yujun Cui, Chengsong Wan, Qinghua Hu
المصدر: Frontiers in Microbiology, Vol 12 (2021)
مصطلحات موضوعية: enterotoxigenic Escherichia coli (ETEC), molecular epidemiology, whole genome sequencing (WGS), virulence factor, antimicrobial resistance (AMR), pathogenicity, Microbiology, QR1-502
الوصف: Enterotoxigenic Escherichia coli (ETEC) is the leading cause of severe diarrhea in children and the most common cause of diarrhea in travelers. However, most ETEC infections in Shenzhen, China were from indigenous adults. In this study, we characterized 106 ETEC isolates from indigenous outpatients with diarrhea (77% were adults aged >20 years) in Shenzhen between 2015 and 2020 by whole-genome sequencing and antimicrobial susceptibility testing. Shenzhen ETEC isolates showed a remarkable high diversity, which belonged to four E. coli phylogroups (A: 71%, B1: 13%, E: 10%, and D: 6%) and 15 ETEC lineages, with L11 (25%, O159:H34/O159:H43, ST218/ST3153), novel L2/4 (21%, O6:H16, ST48), and L4 (15%, O25:H16, ST1491) being major lineages. Heat-stable toxin (ST) was most prevalent (76%, STh: 60% STp: 16%), followed by heat-labile toxin (LT, 17%) and ST + LT (7%). One or multiple colonization factors (CFs) were identified in 68 (64%) isolates, with the common CFs being CS21 (48%) and CS6 (34%). Antimicrobial resistance mutation/gene profiles of genomes were concordant with the phenotype testing results of 52 representative isolates, which revealed high resistance rate to nalidixic acid (71%), ampicillin (69%), and ampicillin/sulbactam (46%), and demonstrated that the novel L2/4 was a multidrug-resistant lineage. This study provides novel insight into the genomic epidemiology and antimicrobial susceptibility profile of ETEC infections in indigenous adults for the first time, which further improves our understanding on ETEC epidemiology and has implications for the development of vaccine and future surveillance and prevention of ETEC infections.
وصف الملف: electronic resource
العلاقة: https://www.frontiersin.org/articles/10.3389/fmicb.2021.732068/fullTest; https://doaj.org/toc/1664-302XTest
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9دورية أكاديمية
المؤلفون: Veronica M. Jarocki, Stefanie Heß, Kay Anantanawat, Thomas U. Berendonk, Steven P. Djordjevic
المصدر: Frontiers in Microbiology, Vol 12 (2021)
مصطلحات موضوعية: Enterotoxigenic Escherichia coli (ETEC), ST182, O169:H41, airplane waste, antimicrobial resistance (AMR), blaCTX–M, Microbiology, QR1-502
الوصف: Enterotoxigenic Escherichia coli (ETEC) is the primary aetiologic agent of traveller’s diarrhoea and a significant cause of diarrhoeal disease and death in developing countries. ETEC O169:H41 strains are known to cause both traveller’s diarrhoea and foodborne outbreaks in developed countries and are cause for concern. Here, whole-genome sequencing (WGS) was used to assemble 46 O169:H41 (ST182) E. coli draft genomes derived from two airplane waste samples sourced from a German international airport. The ST182 genomes were compared with all 84 publicly available, geographically diverse ST182 genomes to construct a core genome-based phylogenetic tree. ST182 isolates were all phylogroup E, the majority serotype O169:H41 (n = 121, 93%) and formed five major clades. The airplane waste isolates differed by an average of 15 core SNPs (range 0–45) but their accessory genome content was diverse. While uncommon in other ST182 genomes, all airplane-derived ST182 isolates carried: (i) extended-spectrum β-lactamase gene blaCTX–M–15 notably lacking the typical adjacent ISEcp1; (ii) qnrS1 and the S83L mutation in gyrA, both conferring resistance to fluoroquinolones; and (iii) a class 1 integron structure (IS26-intI1Δ648-dfrA17-aadA5-qacEΔ1-sul1-ORF-srpC-padR-IS6100-mphR-mrx-mphA-IS26) identified previously in major extraintestinal pathogenic E. coli STs but not in ETEC. ST182 isolates carried ETEC-specific virulence factors STp + CS6. Adhesin/invasin tia was identified in 89% of aircraft ST182 isolates (vs 23%) and was located on a putative genomic island within a hotspot region for various insertions including PAI I536 and plasmid-associated transposons. The most common plasmid replicons in this collection were IncFII (100%; F2:A-:B-) and IncB/O/K/Z (89%). Our data suggest that potentially through travel, E. coli ST182 are evolving a multidrug-resistant profile through the acquisition of class 1 integrons and different plasmids.
وصف الملف: electronic resource
العلاقة: https://www.frontiersin.org/articles/10.3389/fmicb.2021.731050/fullTest; https://doaj.org/toc/1664-302XTest
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10دورية أكاديمية
المؤلفون: Ephrem Debebe Zegeye, Yuleima Diaz, Pål Puntervoll
المصدر: Vaccines, Vol 10, Iss 2, p 241 (2022)
مصطلحات موضوعية: enterotoxigenic Escherichia coli (ETEC), heat-stable enterotoxin (ST), diarrhea, toxoid, vaccine, cross-reaction, Medicine
الوصف: Heat-stable enterotoxin (ST) producing enterotoxigenic Escherichia coli (ETEC) strains are among the top four enteropathogens associated with moderate-to-severe diarrhea in children under five years in low-to-middle income countries, thus making ST a target for an ETEC vaccine. However, ST must be mutated to abolish its enterotoxicity and to prevent a potential immunological cross-reaction due to its structural resemblance to the human peptides uroguanylin and guanylin. To reduce the risk of eliciting cross-reacting antibodies with our lead STh-A14T toxoid, L9 was chosen as an additional mutational target. A double mutant vaccine candidate immunogen, STh-L9A/A14T, was constructed by conjugation to the synthetic virus-like mi3 nanoparticle using the SpyTag/SpyCatcher technology. This immunogen elicited STh neutralizing antibodies in mice, but with less consistency than STh-A14T peptide control immunogens. Moreover, individual sera from mice immunized with both single and double mutant variants displayed varying levels of unwanted cross-reacting antibodies. The lowest levels of cross-reacting antibodies were observed with STh-L9K/A14T control immunogens, suggesting that it is indeed possible to reduce the risk of eliciting cross-reacting antibodies by mutation. However, mutant-specific antibodies were observed for most double mutant immunogens, demonstrating the delicate balancing act between disrupting cross-reacting epitopes, keeping protective ones, and avoiding the formation of neoepitopes.
وصف الملف: electronic resource
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