Our ultimate aim is to characterise proteins, selleck catalog produced by probiotic bacteria, that are resistant to gut enzymes and produce ��homeostatic�� effects on immunity. Such ��natural�� products from commensal bacteria may well have been honed in vivo over millennia to facilitate mutually beneficial interactions between the microbiota and its host. In agreement with that concept we have identified a secreted bacterial peptide, highly resistant to proteolysis by gastrointestinal enzymes, which may play a role in generation of regulatory immune responses in the gut. From an applied point of view, STp may be used as an additive and/or nutraceutical compound and may therefore set the basis for non-drug related dietary treatment for patients with IBD.
Its presence in the gut of healthy individuals, together with its absence in most of the IBD gut samples analysed so far, makes STp-containing proteins as promising biomarkers of healthy gut. Supporting Information Figure S1 Slide 1: Theoretical cleavage sites of the intestinal proteases chymotrypsin, pepsin and trypsin were predicted at the ExPASy proteomic server, using the peptide cutter application (http://expasy.org/tools/peptidecutter/). The ST domain, where no predicted cleavage sites are predicted, is highlighted with the black arrow. (PPT) Click here for additional data file.(111K, ppt) Table S1 Strains and primers used in the present work. * NaeI recognition sites are underlined, and sequence coding for the histidine tag double-underlined. (DOC) Click here for additional data file.(46K, doc) Table S2 antibodies used for flow cytometry.
(XLS) Click here for additional data file.(21K, xls) Acknowledgments Strain NZ9000 and plasmid pNZ8110 were kindly provided by Dr. Oscar Kuipers and Dr. Jan Kok. We kindly thank Dr. C.T. Tee, Dr. J. Landy, Dr. S.T.C. Peake and Dr. A.L. Hart for providing us with the required biological samples from healthy controls. Footnotes Competing Interests: The authors have declared that no competing interests exist. Funding: This work was supported by Juan de la Cierva postdoctoral contract from the Spanish Ministerio de Ciencia e Innovacion (Borja S��nchez), Marie Curie IntraEuropean Fellowship FP7-people-IEF-2008 (David Bernardo); St Mark��s Hospital Foundation, the Brigid Balfour Fund and grants AGL2010-14952 and RM2010-00012-00-00 from the Spanish Ministerio de 1 Ciencia e Innovaci��n.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a tumor-selective, apoptosis-inducing cytokine. By binding to the death receptors DR4 and DR5, TRAIL can recruit the intracellular adaptor molecule, Fas-associated protein with death domain (FADD), to death domains present Brefeldin_A in the cytoplasmic region of these receptors and form a death-inducing signaling complex.