Structural highlights
Publication Abstract from PubMedClostridioides difficile is the primary cause of antibiotic-associated diarrhoea and colitis, a healthcare-associated intestinal disease resulting in a significant fatality rate. Colonization of the gut is critical for C. difficile pathogenesis, and 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 1.80-2.50 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 a effective component in a vaccine against C. difficile. Molecular features of lipoprotein CD0873 - a potential vaccine against the human pathogen Clostridioides difficile.,Bradshaw WJ, Bruxelle JF, Kovacs-Simon A, Harmer NJ, Janoir C, Pechine S, Acharya KR, Michell SL J Biol Chem. 2019 Aug 16. pii: RA119.010120. doi: 10.1074/jbc.RA119.010120. PMID:31420448[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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