Colonization factors of human and animal-specific enterotoxigenic Escherichia coli (ETEC)

Trends in Microbiology, Год журнала: 2023, Номер 32(5), С. 448 - 464

Опубликована: Дек. 4, 2023

Colonization factors (CFs) are major virulence of enterotoxigenic Escherichia coli (ETEC). This pathogen is among the most common causes bacterial diarrhea in children low- and middle-income countries, travelers, livestock. CFs candidate antigens vaccines under development as preventive measures against ETEC infections humans Recent molecular studies have indicated that newly identified on human closely related to animal CFs. Increased knowledge pathogenic mechanisms, immunogenicity, regulation, expression CFs, well possible spread humans, may facilitate future for animals. Here, we present an updated review ETEC.

Язык: Английский

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Genomic insights into the 2022–2023Vibrio cholerae outbreak in Malawi

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июль 26, 2024

Malawi experienced its deadliest Vibrio cholerae (Vc) outbreak following devastating cyclones, with >58,000 cases and >1700 deaths reported between March 2022 May 2023. Here, we use population genomics to investigate the attributes origin of 2022-2023 Vc isolates. Our results demonstrate predominance ST69 clone, also known as seventh cholera pandemic El Tor (7PET) lineage, expressing O1 Ogawa (~ 80%) serotype followed by Inaba 16%) sporadic non-O1/non-7PET serogroups 4%). Phylogenetic reconstruction revealed that strains correspond a recent importation from Asia into Africa (sublineage AFR15). These isolates harboured antimicrobial resistance virulence elements, notably ICE

Язык: Английский

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Targeting Enterotoxins: Advancing Vaccine Development for Enterotoxigenic Escherichia coli ETEC

Toxins, Год журнала: 2025, Номер 17(2), С. 71 - 71

Опубликована: Фев. 6, 2025

Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrheal disease worldwide, particularly in children low- and middle-income countries. Its ability to rapidly colonize the intestinal tract through diverse colonization factors toxins underpins its significant public health impact. Despite extensive research several vaccine candidates reaching clinical trials, no licensed exists for ETEC. This review explores temporal spatial coordination ETEC virulence factors, focusing on interplay between adherence mechanisms toxin production as critical targets therapeutic intervention. Advancements molecular biology host–pathogen interaction studies have uncovered species-specific variations cross-reactivity human animal strains. In particular, heat-labile (LT) heat-stable (ST) provided crucial insights into disruption. Additional exotoxins, such EAST-1 hemolysins, further highlight multifactorial nature pathogenicity. Innovative strategies, including multiepitope fusion antigens (MEFAs), mRNA-based approaches, glycoconjugates, aim enhance broad-spectrum immunity. Novel delivery methods, like intradermal immunization, show promise eliciting robust immune responses. Successful vaccination against will offer an effective affordable solution with potential greatly reduce mortality prevent stunting, representing highly impactful cost-efficient global challenge.

Язык: Английский

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Vaccine Preventable Zoonotic Diseases: Challenges and Opportunities for Public Health Progress

Vaccines, Год журнала: 2022, Номер 10(7), С. 993 - 993

Опубликована: Июнь 22, 2022

Zoonotic diseases represent a heavy global burden, causing important economic losses, impacting animal health and production, costing millions of human lives. The vaccination animals humans to prevent inter-species zoonotic disease transmission is an intervention. However, efforts develop implement vaccine interventions reduce impacts are often limited the veterinary agricultural sectors do not reflect shared burden disease. Multisectoral collaboration, including co-development opportunities for vaccines, expanding use include reservoirs such as wildlife, strategically using vaccines interrupt complex cycles needed. Addressing zoonoses requires multi-faceted One Health approach, wherein vaccinating people plays critical role.

Язык: Английский

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A low-cost recombinant glycoconjugate vaccine confers immunogenicity and protection against enterotoxigenic Escherichia coli infections in mice

Frontiers in Molecular Biosciences, Год журнала: 2023, Номер 10

Опубликована: Март 2, 2023

Enterotoxigenic Escherichia coli (ETEC) is the primary etiologic agent of traveler's diarrhea and a major cause diarrheal disease death worldwide, especially in infants young children. Despite significant efforts over past several decades, an affordable vaccine that appreciably decreases mortality morbidity associated with ETEC infection among children under age 5 years remains unmet aspirational goal. Here, we describe robust, cost-effective biosynthetic routes leverage glycoengineered strains non-pathogenic E. or their cell-free extracts for producing conjugate candidates against two most prevalent O serogroups ETEC, O148 O78. Specifically, demonstrate site-specific installation O-antigen polysaccharides (O-PS) corresponding to these onto licensed carrier proteins using oligosaccharyltransferase PglB from Campylobacter jejuni. The resulting conjugates stimulate strong O-PS-specific humoral responses mice elicit IgG antibodies possess bactericidal activity cognate pathogens. We also show one prototype decorated serogroup O-PS reduces colonization mice, providing evidence vaccine-induced mucosal protection. anticipate our bacterial cell-based platforms will enable creation multivalent formulations potential broad protection increased access through low-cost biomanufacturing.

Язык: Английский

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Assessment of heat-killed E. coli expressing Chikungunya virus E2 protein as a candidate vaccine for dual protection against Chikungunya virus and E. coli

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 7, 2025

The Chikungunya virus (CHIKV) is a mosquito-borne with long history of recurring epidemics transmitted through Aedes mosquitoes. rapid spread CHIKV has intensified the need for potent vaccines. Escherichia coli (E.coli), vital part human gut microbiota, utilized in recombinant DNA technology cloning. However, its high adaptability can lead to severe infections humans. This study aimed develop candidate dual vaccine against and E. coli. For this, we expressed E2 protein Rosetta Bl21 cells expression was confirmed by western blotting. IgG immune response determined ELISA. Further, potential antibodies neutralize evaluated via Tissue Culture Infectious Dose 50 (TCID50). We observed that expressing alum immunized mice serum showed five-fold higher CHIKV, compared control cells. neutralization assay results two-fold decrease TCID50 value after 12 hours three-fold reduction 120 hours. Similarly, formulation also elicited significantly suggested approach generating an both. proposes faster, safer, cost-effective protein-based development.

Язык: Английский

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Characterization of the ligand binding pocket of the virulence regulator Rns, a Member of the AraC/XylS family of transcription factors

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 14, 2025

Abstract Diarrheal disease caused by Gram-negative enteric pathogens such as enterotoxigenic Escherichia coli (ETEC), Vibrio cholerae , Shigella spp. and, Salmonella are a leading cause of morbidity and mortality children; especially, in low resource nations. While progress has been made reducing this burden, there remains need to develop efficacious therapies. Recently, we determined the structure Rns, member AraC/XylS family that regulates expression pili other virulence factors ETEC. The revealed decanoic acid bound between N- C-terminal domains. To test hypothesis directly inhibits used its identify residues necessary for ligand binding. Removal positive side chains R75 H20 rendered Rns insensitive fatty inhibition. Additionally, mutations designed occlude binding also produced variant was insensitive. We observed is structurally more flexible than wildtype with acid; suggesting contributes structural rigidity. These studies precisely demonstrate pocket critical acids inhibition DNA This supports our must bind inhibit AraC regulators. Further work us others suggests regulators common paradigm among many bacterial pathogens. Therefore, understanding molecular basis lays groundwork development small molecule therapeutics targeting disease.

Язык: Английский

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Preparation and Evaluation of Novel Epitope-Based ETEC K88-K99 Bivalent Vaccine

Veterinary Sciences, Год журнала: 2025, Номер 12(4), С. 381 - 381

Опубликована: Апрель 18, 2025

Enterotoxigenic Escherichia coli (ETEC) is one of the primary pathogens causing diarrhea in piglets, significant economic losses swine farming industry. Due to numerous serotypes ETEC, traditional vaccines fail provide sufficient cross-protection, and subunit based on epitope design have emerged as a safer more effective approach for prevention control. Unlike vaccine development strategies that involve tandem arrangement multiple antigenic epitopes, this study used K88-FaeG protein backbone incorporated epitopes K99-FanC achieve better immunogenicity. By using bioinformatics software predict B-cell linear (score over 0.6), from three-dimensional structures (50% amino acid score ≥0.2), IgG antibody subtypes, well docking analysis with Sus scrofa aminopeptidase N (APN) receptors, six were selected. Through Western blotting competitive ELISA, we confirmed all recombinant proteins exhibited binding capabilities K88- K99-positive serum. The ELISA results showed serum levels specific IgA antibodies increased after immunization, FaeG-Ep3 FaeG-Ep5 inducing highest titers against FanC-IgG (Log2 = 14.96) FaeG-IgG 17.96), respectively. Bacterial adhesion assays revealed only effectively blocked both K99 K88 IPEC-J2 cells. Immunization challenge experiments that, unimmunized group, mice infected experienced weight loss (p < 0.05) intestinal villus shedding wall structural damage. However, FaeG-Ep3-immunized no occurred infection, protection rate (83%) was same FaeG FanC immunized groups. Overall, identified shows potential application value provides new insights developing multivalent ETEC.

Язык: Английский

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In silico Designing of an Epitope-Based Vaccine Against Common E. coli Pathotypes

Frontiers in Medicine, Год журнала: 2022, Номер 9

Опубликована: Март 4, 2022

Escherichia coli (E. coli) is a Gram-negative bacterium that belongs to the family Enterobacteriaceae. While E. can stay as an innocuous resident in digestive tract, it cause group of symptoms ranging from diarrhea live threatening complications. Due increased rate antibiotic resistance worldwide, development effective vaccine against pathotypes major health priority. In this study, reverse vaccinology approach along with immunoinformatics has been applied for detection potential antigens develop vaccine. Based on our screening 5,155 proteins, we identified lipopolysaccharide assembly protein (LptD) and outer membrane factor (BamA) candidates current study. The conservancy these proteins main was assessed through BLASTp make sure designed will be protective pathotypes. multitope constructed using cytotoxic T lymphocyte (CTL), helper (HTL), B cell (BCL) epitopes suitable linkers adjuvant. Following that, analyzed computationally where found antigenic, soluble, stable, non-allergen. Additionally, adopted docking well all-atom molecular dynamics simulation, illustrated promising predicted affinity free binding energy human Toll-like receptor-4 (hTLR-4) dimeric state. regard, wet lab studies are required prove efficacy construct demonstrated results computational validation.

Язык: Английский

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Vaccine value profile for enterotoxigenic Escherichia coli (ETEC)

Vaccine, Год журнала: 2023, Номер 41, С. S95 - S113

Опубликована: Окт. 6, 2023

Enterotoxigenic Escherichia coli (ETEC) is one of the leading bacterial causes diarrhoea, especially among children in low-resource settings, and travellers military personnel from high-income countries. WHO's primary strategic goal for ETEC vaccine development to develop a safe, effective, affordable that reduces mortality morbidity due moderate-to-severe diarrhoeal disease infants under 5 years age LMICs, as well long-term negative health impact on infant physical cognitive resulting infection with this enteric pathogen. An effective will also likely reduce need antibiotic treatment help limit further emergence antimicrobial resistance pathogens. The lead candidate, ETVAX, has shown field efficacy moved into testing LMIC children. A Phase 3 study projected start 2024 plans trial are discussion U.S. FDA. Licensing both travel indications be feasible next 5–8 years. Given increasing recognition its child LMICs predominance etiology travellers' diarrhoea (TD), standalone more cost-effective than vaccines targeting other TD pathogens, viable commercial market exists. In contrast, combination an childhood pathogens would maximize protection manner series stand-alone vaccines. This 'Vaccine Value Profile' (VVP) intended provide high-level, holistic assessment available data inform potential public health, economic societal value pipeline vaccine-like products. VVP was developed by working group subject matter experts academia, non-profit organizations, private partnerships, multi-lateral organizations. All contributors have extensive expertise various elements collectively aimed identify current research knowledge gaps. using only existing publicly information.

Язык: Английский

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