induces MST2 phosphorylation mediating the activation of hippo signaling pathway to promote apoptosis and lung tissue damage.

() is an intracellular parasite, and its regulation of host cell apoptosis directly affects its parasitism. Studies link -induced apoptosis to abnormal expression of mammalian STE20-like protein kinase 2 (MST2), but its precise role remains unclear. In this study, the regulatory roles in apoptosis and pathogenicity of infection were identified and .

Differential Adjuvant Activity by Flagellins from , Serotype Typhimurium, and .

(1) : The adjuvant properties of flagellin from various bacterial species have been extensively studied; however, a systematic comparison of the immunoadjuvant effects of flagellins from different bacterial species is lacking. This study aims to analyze the amino acid sequences and structural features of flagellins from (FliC), serotype Typhimurium (FliC), and (FliC), and to evaluate their adjuvant activities in terms of Toll-like receptor 5 (TLR5) activation, antibody production, and cytokine responses in a murine model. (2) : Bioinformatics analysis was conducted to compare the amino acid sequences and structural domains (D0, D1, D2, and D3) of flagellins from the three bacterial species.

Current Progress, Challenges and Prospects in the Development of COVID-19 Vaccines.

The COVID-19 pandemic has resulted in over 772 million confirmed cases, including nearly 7 million deaths, according to the World Health Organization (WHO). Leveraging rapid development, accelerated vaccine approval processes, and large-scale production of various COVID-19 vaccines using different technical platforms, the WHO declared an end to the global health emergency of COVID-19 on May 5, 2023. Current COVID-19 vaccines encompass inactivated, live attenuated, viral vector, protein subunit, nucleic acid (DNA and RNA), and virus-like particle (VLP) vaccines.

Phosphoproteomic analysis reveals changes in A-Raf-related protein phosphorylation in response to Toxoplasma gondii infection in porcine macrophages.

Background: Toxoplasma gondii is an obligate intracellular protozoan parasite that causes severe threats to humans and livestock. Macrophages are the cell type preferentially infected by T. gondii in vivo.

Both LTA and LTB Subunits Are Equally Important to Heat-Labile Enterotoxin (LT)-Enhanced Bacterial Adherence.

There is increasing evidence indicating that the production of heat-labile enterotoxin (LT) enhances bacterial adherence within in vitro and in vivo models. However, which subunit plays the main role, and the precise regulatory mechanisms remain unclear. To further elucidate the contribution of the A subunit of LT (LTA) and the B subunit of LT (LTB) in LT-enhanced bacterial adherence, we generated several LT mutants where their ADP-ribosylation activity or GM1 binding ability was impaired and evaluated their abilities to enhance the two LT-deficient strains (1836-2 and EcNc) adherence.

Safety and protective effects of an avirulent Salmonella Gallinarum isolate as a vaccine candidate against Salmonella Gallinarum infections in young chickens.

Fowl typhoid is an important disease of chickens and turkeys, which is caused by Salmonella Gallinarum (S. Gallinarum). Vaccines with high levels of protective effects against fowl typhoid need to be developed for the poultry industry.

Heat-labile enterotoxin enhances F4-producing enterotoxigenic E. coli adhesion to porcine intestinal epithelial cells by upregulating bacterial adhesins and STb enterotoxin.

As one of the crucial enterotoxins secreted by enterotoxigenic Escherichia coli (ETEC), heat-labile enterotoxin (LT) enhances bacterial adherence both in vivo and in vitro; however, the underlying mechanism remains unclear. To address this, we evaluated the adherence of LT-producing and LT-deficient ETEC strains using the IPEC-J2 cell model. The expression levels of inflammatory cytokines and chemokines, and tight-junction proteins were evaluated in IPEC-J2 cells after infection with various ETEC strains.

Evaluation of Multivalent Enterotoxigenic Vaccine Candidate MecVax Antigen Dose-Dependent Effect in a Murine Model.

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-mnLT, and adhesin CFA/I/II/IV MEFA has not been investigated.

Different serotypes of Escherichia coli flagellin exert identical adjuvant effects.

Bacterial flagellin is a potent powerful adjuvant, which exerts its adjuvant activity by activating the Toll-like receptor 5 (TLR5) signaling pathway to induce host pro-inflammatory responses. Flagellin of Salmonella typhimurium (S. typhimurium) has shown strong adjuvant effects for a variety of vaccine candidates, however, the adjuvanticity of different serotypes of Escherichia coli (E.

Quorum sensing-1 signaling of N-hexanoyl-L-homoserine lactone contributes to virulence in avian pathogenic Escherichia coli.

Avian pathogenic E. coli (APEC) caused avian colibacillosis is mostly common in poultry industry worldwide. APEC virulence factors lead to pathogenesis and the quorum sensing (QS) system is actively involved in the regulation of these virulence factors.

Sef fimbria operon construction, expression, and function for direct rapid detection of Salmonella Enteritidis.

Salmonella Enteritidis (SE) causes both horizontal and vertical transmission of diseases in poultry industry and is also one of the main causes of human food poisoning. Sequence analysis of the sef operon of poultry-derived Salmonella serotypes showed the presence of an entire sef operon in SE, whereas only sef pseudogenes were found in Salmonella Gallinarum and Salmonella Pullorum. Subsequently, the sef operon of SE was cloned into the pBR322 plasmid and expressed in a modified Escherichia coli strain SE5000.

Preclinical Characterization of Immunogenicity and Efficacy against Diarrhea from MecVax, a Multivalent Enterotoxigenic E. coli Vaccine Candidate.

There are no vaccines licensed for enterotoxigenic Escherichia coli (ETEC), a leading cause of diarrhea for children in developing countries and international travelers. Virulence heterogeneity among strains and difficulties identifying safe antigens for protective antibodies against STa, a potent but poorly immunogenic heat-stable toxin which plays a key role in ETEC diarrhea, are challenges in ETEC vaccine development. To overcome these challenges, we applied a toxoid fusion strategy and a novel epitope- and structure-based multiepitope fusion antigen (MEFA) vaccinology platform to construct two chimeric multivalent proteins, toxoid fusion 3xSTa-mnLT and adhesin CFA/I/II/IV MEFA, and demonstrated that the proteins induced protective antibodies against STa and heat-labile toxin (LT) produced by all ETEC strains or the seven most important ETEC adhesins (CFA/I and CS1 to CS6) expressed by the ETEC strains causing 60 to 70% of diarrheal cases and moderate to severe cases.

Use of Fimbrial Rod for F18ab Fimbriae+ STEC Colonization to Host Cells.

Type 1 fimbriae are important virulence determinants of some Gram-negative pathogens, which promote bacterial colonization. The fimbrial rod is primarily composed of multiple copies of the major fimbrial subunit FimA. FimH adhesin, however, is present as a fibrillar tip structure that drive bacteria binding to host cellular mannose containing receptor.

The impact of cell structure, metabolism and group behavior for the survival of bacteria under stress conditions.

Microbes from diverse types of habitats are continuously exposed to external challenges, which may include acidic, alkaline, and toxic metabolites stress as well as nutrient deficiencies. To promote their own survival, bacteria have to rapidly adapt to external perturbations by inducing particular stress responses that typically involve genetic and/or cellular changes. In addition, pathogenic bacteria need to sense and withstand these environmental stresses within a host to establish and maintain infection.

A multivalent vaccine candidate targeting enterotoxigenic Escherichia coli fimbriae for broadly protecting against porcine post-weaning diarrhea.

Fimbriae-mediated initial adherence is the initial and critical step required for enterotoxigenic Escherichia coli (ETEC) infection. Therefore, vaccine candidates have been developed that target these fimbriae and induce specific anti-fimbriae antibodies to block initial ETEC attachment. While this vaccine effectively protects against ETEC-associated post-weaning diarrhea (PWD), developing a broadly effective vaccine against initial ETEC attachment remains a challenging problem, owing to the immunological heterogeneity among these antigens.

Vaccines against gastroenteritis, current progress and challenges.

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.

Coimmunization with Two Enterotoxigenic Escherichia coli (ETEC) Fimbrial Multiepitope Fusion Antigens Induces the Production of Neutralizing Antibodies against Five ETEC Fimbriae (F4, F5, F6, F18, and F41).

Fimbriae mediate the initial adherence of enterotoxigenic (ETEC) to the piglet small intestine and play an important role in development of ETEC-driven postweaning diarrhea (PWD). PWD inflicts huge economic losses on the swine industry each year, making development of alternative treatment and prevention measures for PWD essential. Vaccine candidates that induce antifimbria antibodies that block the initial attachment and colonization of ETEC pathogens with fimbriae are one approach that could help prevent PWD.

Review of Newly Identified Functions Associated With the Heat-Labile Toxin of Enterotoxigenic .

Heat-labile toxin (LT) is a well-characterized powerful enterotoxin produced by enterotoxigenic (ETEC). This toxin is known to contribute to diarrhea in young children in developing countries, international travelers, as well as many different species of young animals. Interestingly, it has also been revealed that LT is involved in other activities in addition to its role in enterotoxicity.

Antibodies induced by enterotoxigenic Escherichia coli (ETEC) adhesin major structural subunit and minor tip adhesin subunit equivalently inhibit bacteria adherence in vitro.

Antibodies that block the adherence of enterotoxigenic Escherichia coli (ETEC) to host intestinal epithelial cells are protective. Multiepitope-fusion-antigens (MEFAs) carrying epitopes of ETEC adhesin major subunits or tip minor subunits induced antibodies against ETEC adherence. Adherence inhibition effectiveness of antibodies induced by major subunit epitopes versus minor tip subunit epitopes, however, has not been comparatively characterized.

Targeting ideal oral vaccine vectors based on probiotics: a systematical view.

Probiotics have great potential to be engineered into oral vaccine delivery systems, which can facilitate elicitation of mucosal immunity without latent risks of pathogenicity. Combined with the progressive understanding of probiotics and the mucosal immune system as well as the advanced biotechniques of genetic engineering, the development of promising oral vaccine vectors based on probiotics is available while complicated and demanding. Therefore, a systematical view on the design of practical probiotic vectors is necessary, which will help to logically analyze and resolve the problems that might be neglected during our exploration.

Immunogenicity characterization of genetically fused or chemically conjugated heat-stable toxin toxoids of enterotoxigenic Escherichia coli in mice and pigs.

Enterotoxigenic Escherichia coli (ETEC) producing type Ib heat-stable toxin (STa) are a main cause of children's diarrhea and travelers' diarrhea, thus STa needs to be targeted in ETEC vaccine development. However, because this 19-amino acid STa is poorly immunogenic, attempts to genetically fuse or chemically couple it to carrier proteins have been made to enhance STa immunogenicity. In this study, we selected one genetic fusion and one chemical conjugate to comparatively evaluate STa immunogenicity.

Co-administered Tag-Less Toxoid Fusion 3xSTa-mnLT and CFA/I/II/IV MEFA (Multiepitope Fusion Antigen) Induce Neutralizing Antibodies to 7 Adhesins (CFA/I, CS1-CS6) and Both Enterotoxins (LT, STa) of Enterotoxigenic (ETEC).

Enterotoxigenic (ETEC) bacteria remain a leading cause of children's diarrhea and travelers' diarrhea. Vaccines that induce antibodies to block ETEC bacterial adherence and to neutralize toxin enterotoxicity can be effective against ETEC-associated diarrhea. Recent studies showed that 6xHis-tagged CFA/I/II/IV multiepitope fusion antigen (MEFA) induced broad-spectrum antibodies to inhibit adherence of the seven most important ETEC adhesins (CFA/I, CS1 to CS6) (Ruan et al.

Significance of Enterotoxigenic Escherichia coli (ETEC) Heat-Labile Toxin (LT) Enzymatic Subunit Epitopes in LT Enterotoxicity and Immunogenicity.

Enterotoxigenic (ETEC) strains producing heat-labile toxin (LT) and/or heat-stable toxin (STa) are a top cause of children's diarrhea and travelers' diarrhea. Holotoxin-structured GM-binding LT is a strong immunogen and an effective adjuvant, and can serve a carrier or a platform for multivalent vaccine development. However, the significance of peptide domains or epitopes of LT particularly enzymatic LT subunit in association with LT enterotoxicity and immunogenicity has not been characterized.