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Characterization of H elicobacter pylori HP 0231 ( DsbK ): role in disulfide bond formation, redox homeostasis and production of H elicobacter cystein‐rich protein HcpE
Author(s) -
Lester Jeffrey,
Kichler Sari,
Oickle Brandon,
Fairweather Spencer,
Oberc Alexander,
Chahal Jaspreet,
Ratnayake Dinath,
Creuzenet Carole
Publication year - 2015
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12923
Subject(s) - disulfide bond , biology , redox , bacteria , biochemistry , chemistry , genetics , organic chemistry
Summary H elicobacter pylori is a human gastric pathogen that colonizes ∼ 50% of the world's population. It can cause gastritis, gastric or duodenal ulcers and also gastric cancer. The numerous side effects of available treatments and the emergence of antibiotic resistant strains are severe concerns that justify further research into H . pylori's pathogenic mechanisms. H . pylori produces secreted proteins that may play a role in virulence, including the H elicobacter cysteine‐rich protein HcpE (aka HP 0235). We demonstrate herein that HcpE is secreted in the culture supernatant both as a soluble protein and in association with outer membrane vesicles. We show that the structure of HcpE comprises an organized array of disulfide bonds. We identify DsbK (aka HP 0231) as a folding factor necessary for HcpE production and secretion in H . pylori and show that recombinant DsbK can interact with and refold unprocessed, reduced HcpE in vitro . These experiments highlight the first biologically relevant substrate for DsbK . Furthermore, we show that DsbK has disulfide bond ( Dsb ) forming activity on reduced lysozyme and demonstrate a DsbA ‐type of activity for DsbK upon expression in E . coli , despite its similarity with DsbG . Finally, we show a role of DsbK in maintaining redox homeostasis in H . pylori .