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J u l y 2 3 - 2 4 , 2 0 1 8 | R o m e , I t a l y
Note:
allied
academies
Joint Event on
Cardiology Congress 2018 & Microbe Infection 2018
Biomedical Research
|
ISSN: 0976-1683
|
Volume 29
2
nd
World Congress on
CARDIOLOGY
MICROBIOLOGY AND MICROBIAL INFECTION
&
39
th
Annual Congress on
Carole Creuzenet, Biomed Res 2018, Volume 29 | DOI: 10.4066/biomedicalresearch-C1-002
HCPE AND DSBK, NOVEL CONTRIBUTORS
TO INFLAMMATION CAUSED BY HUMAN
GASTRIC PATHOGEN
HELICOBACTER
PYLORI
Carole Creuzenet
The University of Western Ontario, Canada
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.
Carole Creuzenet has completed her PhD in Biochem-
istry at the University of Nantes and the National In-
stitute 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 gastroin-
testinal pathogens such as
Campylobacter jejuni, He-
licobacter 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.
ccreuzen@uwo.caBIOGRAPHY