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Pseudomonas fluorescens encodes the Crohn's disease-associated I2 sequence and T-cell superantigen
Bo Wei1, Tiffany Huang, Harnisha Dalwadi
1Department of Pathology, University of California, Los Angeles 90095, USA.
Abstract:
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 I2, a novel gene segment of microbial origin that is associated with human CD and that encodes a T-cell superantigen. To identify the I2 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 I2, with homologues detectable in 3 of 13 other Pseudomonas species. Genomic cloning disclosed a locus containing the full-length I2 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 I2 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.
Insights
Pseudomonas fluorescens harbors the I2 gene (pfiT), a microbial superantigen linked to Crohn's disease (CD). This finding suggests a role for P. fluorescens in CD pathogenesis.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Commensal bacteria are implicated in Crohn's disease (CD) and inflammatory bowel disease (IBD) models.
- A novel microbial gene segment, I2, associated with CD, encodes a T-cell superantigen.
Purpose of the Study:
- To identify the microorganism origin of the I2 gene segment.
- To investigate the role of the I2 gene and its originating species in Crohn's disease pathogenesis.
Main Methods:
- BLAST analysis to identify microbial homologues.
- PCR and Southern analysis to determine the species of origin.
- Genomic cloning to characterize the gene locus.
- Assessing CD4(+) T-cell responses to recombinant proteins.
Main Results:
- The I2 gene originates from Pseudomonas fluorescens, with homologues in other Pseudomonas species.
- The full-length I2 gene, named pfiT, is part of an iron-response gene locus.
- Recombinant I2 and pfiT proteins elicited potent CD4(+) T-cell responses.
- pfiT exhibits characteristics of a virulence factor, including T-cell superantigen activity.
Conclusions:
- Pseudomonas fluorescens and its pfiT gene are suggested to play a role in the pathogenesis of Crohn's disease.
- The T-cell superantigen activity of pfiT may contribute to the immune dysregulation observed in CD.