Mucosal immunity induced by gliadin-presenting spores of Bacillus subtilis in HLA-DQ8-transgenic mice

Bonavita, Roberta; Isticato, Rachele; Maurano, Francesco; Ricca, Ezio; Rossi, Mauro

doi:10.1016/j.imlet.2015.04.005

Cited by 12 publications

(5 citation statements)

References 29 publications

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“…Secondly, the toxic substance derived from E. coli could be prevented from invading the animal’s gastrointestinal tract. Finally, the AMP-producing probiotics not only act as host bacteria for expressing AMPs, but also an important microorganism on regulating microbial ecological balance and immune functions in an animal’s intestinal tract [25,26]. B. subtilis is one of the important probiotics in human and animal gastrointestinal tracts [27], therefore in this study it was selected as a candidate probiotic to generate a derived strain engineered for expressing AMPs.…”

Section: Discussionmentioning

confidence: 99%

Construction of Bacillus subtilis strain engineered for expression of porcine β-defensin-2/cecropin P1 fusion antimicrobial peptides and its growth-promoting effect and antimicrobial activity

Zhong

Zhang

et al. 2016

Asian-Australas J Anim Sci

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ObjectiveTo generate recombinant Bacillus subtilis (B. subtilis) engineered for expression of porcine β-defensin-2 (pBD-2) and cecropin P1 (CP1) fusion antimicrobial peptide and investigate their anti-bacterial activity in vitro and their growth-promoting and disease resisting activity in vivo.MethodsThe pBD-2 and CP1 fused gene was synthesized using the main codons of B. subtilis and inserted into plasmid pMK4 vector to construct their expression vector. The fusion peptide-expressing B. subtilis was constructed by transformation with the vector. The expressed fusion peptide was detected with Western blot. The antimicrobial activity of the expressed fusion peptide and the recovered pBD-2 and CP1 by enterokinase digestion in vitro was analyzed by the bacterial growth-inhibitory activity assay. To analyze the engineered B. subtilis on growth promotion and disease resistance, the weaned piglets were fed with basic diet supplemented with the recombinant B. subtilis. Then the piglets were challenged by enteropathogenic Escherichia coli (E. coli). The weight gain and diarrhea incidence of piglets were measured after challenge.ResultsThe recombinant B. subtilis engineered for expression of pBD-2/CP1 fusion peptide was successfully constructed using the main codons of the B. subtilis. Both expressed pBD-2/CP1 fusion peptide and their individual peptides recovered from parental fusion peptide by enterokinase digestion possessed the antimicrobial activities to a variety of the bacteria, including gram-negative bacteria (E. coli, Salmonella typhimurium, and Haemophilus parasuis) and gram-positive bacteria (Staphylococcus aureus). Supplementing the engineered B. subtilis to the pig feed could significantly promote the piglet growth and reduced diarrhea incidence of the piglets.ConclusionThe generated B. subtilis strain can efficiently express pBD-2/CP1 fusion antimicrobial peptide, the recovered pBD-2 and CP1 peptides possess potent antimicrobial activities to a variety of bacterial species in vitro. Supplementation of the engineered B. subtilis in pig feed obviously promote piglet growth and resistance to the colibacillosis.

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Section: Discussionmentioning

confidence: 99%

Construction of Bacillus subtilis strain engineered for expression of porcine β-defensin-2/cecropin P1 fusion antimicrobial peptides and its growth-promoting effect and antimicrobial activity

Zhong

Zhang

et al. 2016

Asian-Australas J Anim Sci

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“…The release of genetically modified microorganisms into nature and their clearance can sometimes be a drawback. To overcome this issue, a non-recombinant to display antigens on the spore surface was proposed by Huang and collaborators in 2010 [ 136 ], and various model antigens have been efficiently displayed [ 137 , 138 , 139 , 140 , 141 ]. This approach uses spores’ negatively charged and hydrophobic surface layer to adsorb foreign proteins, and is more efficient at acidic pH [ 85 , 142 , 143 , 144 ].…”

Section: Bacterial Spores As a Mucosal Vaccine Delivery Systemmentioning

confidence: 99%

Bacterial Spore-Based Delivery System: 20 Years of a Versatile Approach for Innovative Vaccines

Isticato

2023

Biomolecules

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Mucosal vaccines offer several advantages over injectable conventional vaccines, such as the induction of adaptive immunity, with secretory IgA production at the entry site of most pathogens, and needle-less vaccinations. Despite their potential, only a few mucosal vaccines are currently used. Developing new effective mucosal vaccines strongly relies on identifying innovative antigens, efficient adjuvants, and delivery systems. Several approaches based on phages, bacteria, or nanoparticles have been proposed to deliver antigens to mucosal surfaces. Bacterial spores have also been considered antigen vehicles, and various antigens have been successfully exposed on their surface. Due to their peculiar structure, spores conjugate the advantages of live microorganisms with synthetic nanoparticles. When mucosally administered, spores expressing antigens have been shown to induce antigen-specific, protective immune responses. This review accounts for recent progress in the formulation of spore-based mucosal vaccines, describing a spore’s structure, specifically the spore surface, and the diverse approaches developed to improve its efficiency as a vehicle for heterologous antigen presentation.

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“…The spore-adsorbed gliadin activated the dendritic cells and elicited a T-cell response in the gut. This mechanism (121) can be utilized for developing immune tolerance.…”

Section: Novel Therapies For Celiac Diseasementioning

confidence: 99%

Evolving Therapy for Celiac Disease

Yoosuf

Makharia

2019

Front. Pediatr.

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Gluten is known to be the main triggering factor for celiac disease (CeD), an immune-mediated disorder. CeD is therefore managed using a strict and lifelong gluten-free diet (GFD), the only effective treatment available currently. However, the GFD is restrictive. Hence, efforts are being made to explore alternative therapies. Based on their mechanisms of action on various molecular targets involved in the pathogenesis of CeD, these therapies may be classified into one of the following five broad approaches. The first approach focuses on decreasing the immunogenic content of gluten, using strategies like genetically modified wheat, intra-intestinal gluten digestion using glutenases, microwave thermal treatment of hydrated wheat kernels, and gluten pretreatment with either bacterial/ fungal derived endopeptidases or microbial transglutaminase. The second approach involves sequestering gluten in the gut lumen before it is digested into immunogenic peptides and absorbed, using binder drugs like polymer p(HEMA-co-SS), single chain fragment variable (scFv), and anti- gluten antibody AGY. The third approach aims to prevent uptake of digested gluten through intestinal epithelial tight junctions, using a zonulin antagonist. The fourth approach involves tissue transglutaminase (tTG) inhibitors to prevent the enhancement of immunogenicity of digested gluten by the intestinal tTG enzyme. The fifth approach seeks to prevent downstream immune activation after uptake of gluten immunogenic peptides through the intestinal mucosal epithelial layer. Examples include HLA-DQ2 blockers that prevent presentation of gluten derived- antigens by dendritic cells to T cells, immune- tolerizing therapies like the vaccine Nexvax2 and TIMP-Glia, cathepsin inhibitors, immunosuppressants like corticosteroids, azathioprine etc., and anti-cytokine agents targeting TNF-α and interleukin-15. Apart from these approaches, research is being done to evaluate the effectiveness of probiotics/prebiotics, helminth therapy using Necator americanus , low FODMAP diet, and pancreatic enzyme supplementation in CeD symptom control; however, the mechanisms by which they play a beneficial role in CeD are yet to be clearly established. Overall, although many therapies being explored are still in the pre-clinical phase, some like the zonulin antagonist, immune tolerizing therapies and glutenases have reached phase II/III clinical trials. While these potential options appear exciting, currently they may at best be used to supplement rather than supplant the GFD.

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Mucosal immunity induced by gliadin-presenting spores of Bacillus subtilis in HLA-DQ8-transgenic mice

Cited by 12 publications

References 29 publications

Construction of Bacillus subtilis strain engineered for expression of porcine β-defensin-2/cecropin P1 fusion antimicrobial peptides and its growth-promoting effect and antimicrobial activity

Construction of Bacillus subtilis strain engineered for expression of porcine β-defensin-2/cecropin P1 fusion antimicrobial peptides and its growth-promoting effect and antimicrobial activity

Bacterial Spore-Based Delivery System: 20 Years of a Versatile Approach for Innovative Vaccines

Evolving Therapy for Celiac Disease

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