Molecular features of lipoprotein CD0873: A potential vaccine against the human pathogen Clostridioides difficile
| Autor: | Nicholas J. Harmer, Andrea Kovacs-Simon, Séverine Péchiné, Claire Janoir, Jean François Bruxelle, William J. Bradshaw, K. Ravi Acharya, Stephen L. Michell |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Lipoproteins Colony Count Microbial Human pathogen Biology Ligands Biochemistry Microbiology Pathogenesis 03 medical and health sciences Immune system vaccine medicine Animals Humans Colonization Colitis protein structure crystallography Molecular Biology Pathogen 030102 biochemistry & molecular biology Clostridioides difficile microbiology Cell Biology medicine.disease Recombinant Proteins Bacterial adhesin tyrosine metabolism Intestines Mice Inbred C57BL Disease Models Animal 030104 developmental biology Immunization Protein Structure and Folding Bacterial Vaccines Immunoglobulin A Secretory Mutation Clostridium Infections Female ABC transporter |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 1083-351X 0021-9258 |
| Popis: | Clostridioides difficile is the primary cause of antibiotic-associated diarrhea and colitis, a healthcare-associated intestinal disease resulting in a significant fatality rate. Colonization of the gut is critical for C. difficile pathogenesis. The bacterial molecules essential for efficient colonization therefore offer great potential as vaccine candidates. Here we present findings demonstrating that the C. difficile immunogenic lipoprotein CD0873 plays a critical role in pathogen success in vivo. We found that in a dixenic colonization model, a CD0873-positive strain of C. difficile significantly outcompeted a CD0873-negative strain. Immunization of mice with recombinant CD0873 prevented long-term gut colonization and was correlated with a strong secretory IgA immune response. We further present high-resolution crystal structures of CD0873, at 1.35–2.50 A resolutions, offering a first view of the ligand-binding pocket of CD0873 and provide evidence that this lipoprotein adhesin is part of a tyrosine import system, an amino acid key in C. difficile infection. These findings suggest that CD0873 could serve as an effective component in a vaccine against C. difficile. |
| Databáze: | OpenAIRE |
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