Advanced

Moonlighting of Helicobacter pylori catalase protects against complement-mediated killing by utilising the host molecule vitronectin

Richter, Corinna LU ; Mukherjee, Oindrilla LU ; Ermert, David LU ; Singh, Birendra LU ; Su, Yu Ching; Agarwal, Vaibhav LU ; Blom, Anna M. LU and Riesbeck, Kristian LU (2016) In Scientific Reports 6.
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
6
publisher
Nature Publishing Group
external identifiers
  • Scopus:84973127098
  • WOS:000374227800001
ISSN
2045-2322
DOI
10.1038/srep24391
language
English
LU publication?
yes
id
7ad5f90a-94c1-4c5e-b086-8e73a88d96b6
date added to LUP
2016-06-30 13:22:20
date last changed
2017-02-06 09:44:56
@article{7ad5f90a-94c1-4c5e-b086-8e73a88d96b6,
  abstract     = {<p>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.</p>},
  articleno    = {24391},
  author       = {Richter, Corinna and Mukherjee, Oindrilla and Ermert, David and Singh, Birendra and Su, Yu Ching and Agarwal, Vaibhav and Blom, Anna M. and Riesbeck, Kristian},
  issn         = {2045-2322},
  language     = {eng},
  month        = {04},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Moonlighting of Helicobacter pylori catalase protects against complement-mediated killing by utilising the host molecule vitronectin},
  url          = {http://dx.doi.org/10.1038/srep24391},
  volume       = {6},
  year         = {2016},
}