Pseudomonas fluorescens encodes the Crohn's disease-associated I2 sequence and T-cell superantigen.
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.
Wei
Bo
B
Department of Pathology, University of California, Los Angeles 90095, USA.
Huang
Tiffany
T
Dalwadi
Harnisha
H
Sutton
Christopher L
CL
Bruckner
David
D
Braun
Jonathan
J
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003001:Cloning, Molecular; D003424:Crohn Disease / Q000276:immunology* / Q000503:physiopathology; D005243:Feces / Q000382:microbiology; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011551:Pseudomonas fluorescens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D018089:Superantigens / Q000737:chemistry / Q000235:genetics* / Q000276:immunology
D001426:Bacterial Proteins; C469916:PfiT protein, Pseudomonas fluorescens; D018089:Superantigens