Biomedical Research

HCPE AND DSBK, NOVEL CONTRIBUTORS TO INFLAMMATION CAUSED BY HUMAN GASTRIC PATHOGEN HELICOBACTER PYLORI

Joint Event on 2^nd World Congress on CARDIOLOGY & 39^th Annual Congress on MICROBIOLOGY AND MICROBIAL INFECTION
July 23-24, 2018 | Rome , Italy

Carole Creuzenet

The University of Western Ontario, Canada

Scientific Tracks Abstracts : Biomed Res

DOI: 10.4066/biomedicalresearch-C1-002

Abstract:

H. pylori causes gastritis, gastric ulcers and cancers but the mechanisms of virulence are not fully understood. It produces secreted proteins which may play a role in eliciting gastric inflammation, including the Helicobacter cysteine rich protein HcpE (HP0235) whose biological function is unknown. Our goal was to investigate if HcpE is secreted by H. pylori and is involved in host/pathogen interactions and identify components essential for its production. Using a combination of anti-HcpE ELISA and Western blots, knockout mutagenesis, phenotypic analyses and biochemical assays, we demonstrate that HcpE is secreted by many strains as a soluble protein and in association with outer membrane vesicles. We show that infected patients produce anti-HcpE antibodies, indicating in situ HcpE production. We show that HcpE comprises many disulfide bonds and identify DsbK (HP0231) as a folding factor necessary for HcpE production, and show that recombinant DsbK can refold unprocessed, reduced HcpE in vitro. This highlights the first biologically relevant substrate for DsbK. Furthermore, we show that DsbK has DiSulfide Bond (Dsb) forming activity and has DsbA-like activity despite its similarity with DsbG. Also, we show a role of DsbK in redox homeostasis in H. pylori. Finally, we show an important role for DsbK and HcpE in host-pathogen interactions, including murine gastric colonization and pro-inflammatory cytokine production in human gastric explants, gastric cell lines and in murine splenocytes. Both proteins will be investigated as therapeutic targets to treat H. pylori infections and prevent gastric ulcers and cancers.

Biography:

Carole Creuzenet has completed her PhD in Biochemistry at the University of Nantes and the National Institute for Agronomical Research (France) and her postdoctoral studies at the Massachusetts Institute of Technology (USA) and the University of Guelph (Canada). She is Associate Professor at the University of Western Ontario (London, Canada), where her lab focuses on virulence factors from bacterial gastrointestinal pathogens such as Campylobacter jejuni, Helicobacter pylori and Yersinia pseudotuberculosis. Her focus is on glycolipids and glycoproteins as well as on novel secreted proteins and their folding partners. She has published 38 papers in reputed journals with h-index of 19.

E-mail: ccreuzen@uwo.ca

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