A5068482377- Probiotics and Fermented Foods
- Diabetes and associated disorders
- Gut microbiota and health
- Infant Nutrition and Health
- Helicobacter pylori-related gastroenterology studies
- Cancer Research and Treatments
- Pancreatic function and diabetes
- Digestive system and related health
- Transgenic Plants and Applications
- Bacterial Genetics and Biotechnology
- Diabetes Management and Research
- Microscopic Colitis
- Clostridium difficile and Clostridium perfringens research
- Inflammatory Bowel Disease
- Microbial Metabolites in Food Biotechnology
- Viral gastroenteritis research and epidemiology
- Bacteriophages and microbial interactions
- IL-33, ST2, and ILC Pathways
- Escherichia coli research studies
- Viral Infectious Diseases and Gene Expression in Insects
- RNA and protein synthesis mechanisms
- Psoriasis: Treatment and Pathogenesis
- Glycosylation and Glycoproteins Research
- Cytokine Signaling Pathways and Interactions
- Immune Cell Function and Interaction
ActoGeniX (Belgium)
2009-2015
Brigham and Women's Hospital
2009
University College Cork
2003-2007
Ghent University
1993-2006
Vlaams Instituut voor Biotechnologie
1998-2006
VIB-UGent Center for Medical Biotechnology
2004
MRC Laboratory of Molecular Biology
1994-1995
The cytokine interleukin-10 (IL-10) has shown promise in clinical trials for treatment of inflammatory bowel disease (IBD). Using two mouse models, we show that the therapeutic dose IL-10 can be reduced by localized delivery a bacterium genetically engineered to secrete cytokine. Intragastric administration IL-10–secreting Lactococcus lactis caused 50% reduction colitis mice treated with dextran sulfate sodium and prevented onset −/− mice. This approach may lead better methods cost-effective...
ABSTRACT Lactococcus lactis is a nonpathogenic and noncolonizing bacterium which being developed as vaccine delivery vehicle for immunization by mucosal routes. To determine whether lactococci can also deliver cytokines to the immune system, we have constructed novel constitutive expression strains of L. accumulate test antigen, tetanus toxin fragment C (TTFC), within cytoplasmic compartment secrete either murine interleukin-2 (IL-2) or IL-6. When mice were immunized intranasally with...
Current interventions for arresting autoimmune diabetes have yet to strike the balance between sufficient efficacy, minimal side effects, and lack of generalized immunosuppression. Introduction antigen via gut represents an appealing method induction antigen-specific tolerance. Here, we developed a strategy tolerance restoration using mucosal delivery in mice biologically contained Lactococcus lactis genetically modified secrete whole proinsulin autoantigen along with immunomodulatory...
Growing insight into the pathogenesis of type 1 diabetes (T1D) and numerous studies in preclinical models highlight potential antigen-specific approaches to restore tolerance efficiently safely. Oral administration protein antigens is a preferred method for induction, but degradation during gastrointestinal passage can impede such protein-based therapies, reducing their efficacy making them cost-ineffective. To overcome these limitations, we generated tolerogenic bacterial delivery...
Abstract Aims/hypothesis We hypothesised that islet beta cell antigen presentation in the gut along with a tolerising cytokine would lead to antigen-specific tolerance type 1 diabetes. evaluated this parallel open-label Phase 1b study using oral AG019, food-grade Lactococcus lactis bacteria genetically modified express human proinsulin and IL-10, as monotherapy parallel, randomised, double-blind 2a AG019 combination teplizumab. Methods Adults (18–42 years) adolescents (12–17 diabetes...
ABSTRACT Surface proteins are important factors in the interaction of probiotic and pathogenic bacteria with their environment or host. We performed a comparative bioinformatic analysis four publicly available Lactobacillus genomes genome salivarius subsp. strain UCC118 to identify secreted those linked cell wall. Proteins were identified which predicted be anchored by WXL-binding domains, N- C-terminal anchors, GW repeats, lipoprotein LysM-binding domains. 10 sortase-dependent surface L....
ABSTRACT The apuB gene of Bifidobacterium breve UCC2003 was shown to encode an extracellular amylopullulanase. ApuB is composed a distinct N-terminally located α-amylase-containing domain which hydrolyzes α-1,4-glucosidic linkages in starch and related polysaccharides C-terminally pullulanase-containing α-1,6 pullulan, allowing the classification this enzyme as bifunctional class II pullulanase. A knockout mutation B. rendered resulting mutant incapable growth medium containing starch,...
The introduction of β-cell autoantigens via the gut through Lactococcus lactis (L. lactis) has been demonstrated to be a promising approach for diabetes reversal in NOD mice. Here we show that combination therapy low-dose anti-CD3 with clinical-grade self-containing L. lactis, appropriate human application, secreting proinsulin and interleukin-10, cured 66% mice new-onset diabetes, which is comparable results plasmid-driven lactis. Initial blood glucose concentrations (<350 mg/dL)...
Secretion of functional recombinant murine interleukin-2 (mIL2) by Lactococcus lactis was achieved fusion the sequence encoding mature mIL2 to secretion signal leader lactococcal usp45 gene placed under transcriptional control phage T7 promoter-T7 RNA polymerase expression system. The one only a few proteins which accumulated in growth medium. Sequence analysis revealed correct processing at first amino acid protein. A T-cell proliferation assay showed that protein has same specific...
ABSTRACT Interleukin-10 (IL-10) is a promising candidate for the treatment of inflammatory bowel disease. Intragastric administration Lactococcus lactis genetically modified to secrete IL-10 in situ intestine was shown be effective healing and preventing chronic colitis mice. However, its use humans hindered by sensitivity L. freeze-drying poor survival gastrointestinal tract. We expressed trehalose synthesizing genes from Escherichia coli under control nisin-inducible promoter . Induced...
A combination treatment (CT) of proinsulin and IL-10 orally delivered via genetically modified Lactococcus lactis bacteria combined with low-dose anti-CD3 (aCD3) therapy successfully restores glucose homeostasis in newly diagnosed non-obese diabetic (NOD) mice. Tolerance is accompanied by the accumulation Foxp3+ regulatory T cells (Tregs) pancreas. To test potential this outside window acute diabetes diagnosis, we substituted autoimmune mice, disease durations varying between 4 53 days,...
In this study, we showed that the cell wall anchor of protein A from Staphylococcus aureus is functional in food-grade organism Lactococcus lactis. fusion composed lactococcal Usp45 secretion signal peptide, streptavidin monomer, and S. became covalently attached to peptidoglycan when expressed L. The moiety was functionally exposed at cellular surface. lactis cells expressing anchored polypeptide could be specifically immobilized on a biotinylated alkaline phosphatase-coated polystyrene support.