ArticleInfection and immunity2016
Neutralization of Clostridium difficile Toxin B Mediated by Engineered Lactobacilli That Produce Single-Domain Antibodies.
Article in Infection and immunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 68 citations in OpenAlex.
- Monoclonal Antibodies Targeting Bacterial Infections: A Broad Review of the Field.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- From lab to law: emerging applications, potential benefits, evolving regulatory framework and challenges for engineered probiotics.Microbial cell factories · 2026Review
- Robust high-sensitivity real-time impedance analysis for neutralization drug screening and toxicity kinetics ofFrontiers in microbiology · 2026Article
- Review
- The microbiota-gut-brain-axis theory: role of gut microbiota modulators (GMMs) in gastrointestinal, neurological, and mental health disorders.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- A genetic safeguard for eliminating target genes in synthetic probiotics in a gut environment.iScience · 2025Article
- Prevention and treatment of antibiotics-associated adverse effects through the use of probiotics: A review.Journal of advanced research · 2025Review
- Small but Mighty: Nanobodies in the Fight Against Infectious Diseases.Biomolecules · 2025Review
- Bioengineered Probiotics for Clostridioides difficile Infection: An Overview of the Challenges and Potential for This New Treatment Approach.Probiotics and antimicrobial proteins · 2025Review
- Metabolic engineering of Lactobacilli spp. for disease treatment.Microbial cell factories · 2025Review
- Fit-for-purpose heterodivalent single-domain antibody for gastrointestinal targeting of toxin B from Clostridium difficile.Protein science : a publication of the Protein Society · 2024Article
- Nanobodies in the fight against infectious diseases: repurposing nature's tiny weapons.World journal of microbiology & biotechnology · 2024Review
- Similarities in Structure and Function of UDP-Glycosyltransferase Homologs from Human and Plants.International journal of molecular sciences · 2024Review
- Probiotics for Prevention and Treatment of Clostridium difficile Infection.Advances in experimental medicine and biology · 2024Article
- Immunization Strategies Against Clostridioides difficile.Advances in experimental medicine and biology · 2024Review
- Therapeutic Approach Targeting Gut Microbiome in Gastrointestinal Infectious Diseases.International journal of molecular sciences · 2023Review
- Development and characterization of phage display-derived anti-toxin antibodies neutralizing TcdA and TcdB ofMicrobiology spectrum · 2023Article
- Mucosal Vaccination Strategies againstVaccines · 2023Review
- Enteric pharmacokinetics of monomeric and multimeric camelid nanobody single-domain antibodies.PloS one · 2023Article
- Lactobacilli as a Vector for Delivery of Nanobodies against Norovirus Infection.Pharmaceutics · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clostridium difficile is the primary cause of nosocomial antibiotic-associated diarrhea in the Western world. The major virulence factors of C. difficile are two exotoxins, toxin A (TcdA) and toxin B (TcdB), which cause extensive colonic inflammation and epithelial damage manifested by episodes of diarrhea. In this study, we explored the basis for an oral antitoxin strategy based on engineered Lactobacillus strains expressing TcdB-neutralizing antibody fragments in the gastrointestinal tract. Variable domain of heavy chain-only (VHH) antibodies were raised in llamas by immunization with the complete TcdB toxin. Four unique VHH fragments neutralizing TcdB in vitro were isolated. When these VHH fragments were expressed in either secreted or cell wall-anchored form in Lactobacillus paracasei BL23, they were able to neutralize the cytotoxic effect of the toxin in an in vitro cell-based assay. Prophylactic treatment with a combination of two strains of engineered L. paracasei BL23 expressing two neutralizing anti-TcdB VHH fragments (VHH-B2 and VHH-G3) delayed killing in a hamster protection model where the animals were challenged with spores of a TcdA(-) TcdB(+) strain of C. difficile (P < 0.05). Half of the hamsters in the treated group survived until the termination of the experiment at day 5 and showed either no damage or limited inflammation of the colonic mucosa despite having been colonized with C. difficile for up to 4 days. The protective effect in the hamster model suggests that the strategy could be explored as a supplement to existing therapies for patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.