Journal
INFECTION AND IMMUNITY
Volume 70, Issue 12, Pages 6567-6575Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.70.12.6567-6575.2002
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- NIDDK NIH HHS [DK46763, P01 DK046763] Funding Source: Medline
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Commensal bacteria have emerged as an important disease factor in human Crohn's disease (CD) and murine inflammatory bowel disease (IBD) models. We recently isolated 12, a novel gene segment of microbial origin that is associated with human CD and that encodes a T-cell superantigen. To identify the 12 microorganism, BLAST analysis was used to identify a microbial homologue, PA2885, a novel open reading frame (ORF) in the Pseudomonas aeruginosa genome. PCR and Southern analysis identified Pseudomonas fluorescens as the originating species of 12, with homologues detectable in 3 of 13 other Pseudomonas species. Genomic cloning disclosed a locus containing the full-length 12 gene (pfiT) and three other orthologous genes, including a homologue of the pbrA/pvdS iron response gene. CD4(+) T-cell responses to recombinant proteins were potent for 12 and pfiT, but modest for PA2885. pfiT has several features of a virulence factor: association with an iron-response locus, restricted species distribution, and T-cell superantigen bioactivity. These findings suggest roles for pfiT and P. fluorescens in the pathogenesis of Crohn's disease.
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