Moonlighting of Helicobacter pylori catalase protects against complement-mediated killing by utilising the host molecule vitronectin
(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.
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- author
- Richter, Corinna LU ; Mukherjee, Oindrilla LU ; Ermert, David LU ; Singh, Birendra LU ; Su, Yu Ching LU ; Agarwal, Vaibhav LU ; Blom, Anna M. LU and Riesbeck, Kristian LU
- organization
- publishing date
- 2016-04-18
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 6
- article number
- 24391
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:84973127098
- pmid:27087644
- 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
- 2024-08-23 17:32:11
@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>}}, 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}}, doi = {{10.1038/srep24391}}, volume = {{6}}, year = {{2016}}, }