Low molecular weight proteins of outer membrane of Salmonella typhimurium are immunogenic in Salmonella induced reactive arthritis revealed by proteomics

Abstract

SummaryIn patients with reactive arthritis (ReA)/undifferentiated spondyloarthropathy (uSpA), synovial fluid mononuclear cells (SFMC) show proliferation to bacterial antigens that trigger ReA, i.e. Chlamydia, Yersinia, Campylobactor, Shigella and Salmonella species. We have shown previously that SFMC proliferate significantly to outer membrane proteins of S typhimurium in Salmonella induced ReA. In the present study we characterized the immunoreactive fractions of outer membrane protein (Omp) of S typhimurium in Salmonella induced ReA. Omp of Salmonella was isolated and fractionated by continuous elution sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) using Prep-Cell into eight Omp fractions based on molecular weight. Twenty-three patients with ReA were screened for the bacterial trigger using the SFMC proliferative response to crude lysates of Y enterocolitica, S flexneri, C jejuni and S typhimurium using thymidine uptake assay. SFMC from patients with salmonella induced ReA were tested against eight fractions. Seven of 23 patients with ReA had S typhimuriuminduced ReA. Of these seven patients, five patients SFMC had a significant stimulation index (SI) against < 22, 22-26, 25-35 and 28-40 kDa fractions of Omp. These fractions were analysed by SDS-PAGE and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, which revealed 10 proteins. These proteins were 37 kDa OmpA, 33 kDa TsX, 28 kDa putative Omp, 28 kDa Vac J, 39 kDa OmpD, 18 kDa OmpX, 23 kDa OmpW, 43 kDa OmpS1 and 19 kDa peptidoglycan-associated lipoprotein. In conclusion, for the first time we have identified some low molecular weight proteins in the Omps of Salmonella which are T cells immunoreactive in patients with salmonella induced ReA/uSpA.

Eight Stranded &beta; -Barrel and Related Outer Membrane Proteins: Role in Bacterial Pathogenesis

“…Like OmpA, OmpW is immunogenic in Salmonella induced reactive arthritis; all fractions producing immunoproliferative responses contained OmpA and OmpW [46]. Sixty percent of Celiac disease patients were seropositive for Bacterioides OmpW antibodies [67], and serum levels decreased significantly when patents were on a gluten free diet [68].…”

“…OmpA is among a number of low molecular weight immunogenic proteins in Salmonella-induced reactive arthritis [46]. In typhoid fever, the immune response is also directed against porins and OmpA [47][48][49].…”

Linocin and OmpW Are Involved in Attachment of the Cystic Fibrosis-Associated Pathogen Burkholderia cepacia Complex to Lung Epithelial Cells and Protect Mice against Infection

“…OmpW proteins have been associated with the attachment of Vibrio alginolyticus; OmpWdeficient mutants showed a 10-fold reduction in mouse colonization (50). OmpW was recently identified as being related to the immune response in inflammatory bowel disease associated with an oral pathogen, Porphyromonas gingivalis (51), and is immunogenic in Salmonella-induced reactive arthritis (52). We have recently shown that immunization of mice with OmpW also protects against B. pseudomallei infection (W. T. Casey, N. Spink, F. Cia, C. Collins, M. Romano, R. Berisio, G. J. Bancroft, and S. McClean, submitted for publication).…”

Reactive Arthritis: A Review

“…Components of triggering bacteria including nucleic acids and protein have been identified in the synovium and in circulatory monocytes of patients diagnosed with ReA [14]. It is not clear how and in what form the bacterial components reach the joint and whether there are viable bacteria in the joint.…”