Identification, immunogenicity, and cross-reactivity of type IV pilin and pilin-like proteins fromClostridium difficile
Year: 2014
Type: article
Abstract: The Gram positive anaerobe Clostridium difficile is the major cause of nosocomial diarrhea; manifestations of infection include diarrhea, pseudomembranous colitis, and death. Genes for type IV pili, a bacterial nanofiber often involved in colonization and until relatively recently described only in Gram negatives, are present in all members of the Clostridiales. We hypothesized that any pilins encoded in the C. difficile genome would be immunogenic, as has been shown with pilins from Gram negative organisms. We describe nine pilin or pilin like protein genes, for which we introduce a coherent nomenclature, in the C. difficile R20291 genome. The nine predicted pilin or pilin like proteins have relatively conserved N terminal hydrophobic regions, but diverge at their C termini. Analysis of synonymous and nonsynonymous substitutions revealed evidence of diversifying selective pressure in two pilin genes. Six of the nine identified proteins were purified and used to immunize mice. Immunization of mice with each individual protein generated antibody responses that varied in titer and cross reactivity, a notable result given the low amino acid sequence identity among the pilins. Further studies in other small mammals mirrored our results in mice. Our results illuminate components of the C. difficile type IV pilus and help identify targets for an anti C. difficile vaccine. Type IV pilins of Clostridium difficile: We describe nine type IV pilins or pilin-like proteins identified in the genome of C. difficile. These proteins have relatively conserved N terminal regions, but diverge at the C termini. Analysis of synonymous and nonsynonymous substitutions indicates two pilin proteins contain codons under positive selection. Immunization of mice with six of the pilins resulted in generation of antibodies with varying titer and crossreactivity.
Source: Pathogens and Disease
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2097077186