title: Moonlighting of Helicobacter pylori catalase protects against complement-mediated killing by utilising the host molecule vitronectin.
abstract: Helicobacter pylori is an important human pathogen and a common cause of peptic ulcers and gastric cancer. Despite H. pylori provoking strong innate and adaptive immune responses, the bacterium is able to successfully establish long-term infections. Vitronectin (Vn), a component of both the extracellular matrix and plasma, is involved in many physiological processes, including regulation of the complement system. The aim of this study was to define a receptor in H. pylori that binds Vn and determine the significance of the interaction for virulence. Surprisingly, by using proteomics, we found that the hydrogen peroxide-neutralizing enzyme catalase KatA is a major Vn-binding protein. Deletion of the katA gene in three different strains resulted in impaired binding of Vn. Recombinant KatA was generated and shown to bind with high affinity to a region between heparin-binding domain 2 and 3 of Vn that differs from previously characterised bacterial binding sites on the molecule. In terms of function, KatA protected H. pylori from complement-mediated killing in a Vn-dependent manner. Taken together, the virulence factor KatA is a Vn-binding protein that moonlights on the surface of H. pylori to promote bacterial evasion of host innate immunity.
authors.affiliation: Clinical Microbiology, Department of Translational Medicine, Lund University, SE-205 02 Malmö, Sweden.
authors.forename: Corinna
authors.initials: C
authors.lastname: Richter
authors.affiliation: Clinical Microbiology, Department of Translational Medicine, Lund University, SE-205 02 Malmö, Sweden.
authors.forename: Oindrilla
authors.initials: O
authors.lastname: Mukherjee
authors.affiliation: Medical Protein Chemistry, Department of Translational Medicine, Lund University, SE-205 02 Malmö, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Ermert
authors.affiliation: Clinical Microbiology, Department of Translational Medicine, Lund University, SE-205 02 Malmö, Sweden.
authors.forename: Birendra
authors.initials: B
authors.lastname: Singh
authors.affiliation: Clinical Microbiology, Department of Translational Medicine, Lund University, SE-205 02 Malmö, Sweden.
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Su
authors.affiliation: Medical Protein Chemistry, Department of Translational Medicine, Lund University, SE-205 02 Malmö, Sweden.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Agarwal
authors.affiliation: Medical Protein Chemistry, Department of Translational Medicine, Lund University, SE-205 02 Malmö, Sweden.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Blom
authors.affiliation: Clinical Microbiology, Department of Translational Medicine, Lund University, SE-205 02 Malmö, Sweden.
authors.forename: Kristian
authors.initials: K
authors.lastname: Riesbeck
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D003165:Complement System Proteins / Q000378:metabolism*; D017353:Gene Deletion; D016480:Helicobacter pylori / Q000201:enzymology* / Q000276:immunology; D057131:Immune Evasion; D007113:Immunity, Innate; D011485:Protein Binding; D014774:Virulence; D037521:Virulence Factors / Q000737:chemistry / Q000378:metabolism*; D019096:Vitronectin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors; D019096:Vitronectin; D003165:Complement System Proteins; D002374:Catalase