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.

Helicobacter pylori Outer Membrane Vesicles Protect the Pathogen From Reactive Oxygen Species of the Respiratory Burst

“…Kata gene (Genbank Accession Number: CP001217 ; encodes KatA) deletion was performed as previously described ( Richter et al, 2016 ). A linear katA-knockout construct containing cat (AY219687.1) was inserted between upstream and downstream flanking regions of the katA gene.…”

“…In order to survive against the highly acidic gastric juice (pH 1.0–3.0), H. pylori uses a series of acidic acclimation systems that neutralize the surrounding acid. Other virulence mechanisms include expression of abundant molecules at the surface for attachment and manipulation of host extracellular matrix proteins and serum resistance ( Parker and Keenan, 2012 ; Richter et al, 2016 ). In addition, H. pylori is equipped with antioxidant molecules such as catalase (KatA), catalase-like protein (KatB), alkyl hydroperoxide reductase (AhpC), and superoxide dismutase (SOD) to detoxify reactive oxygen species (ROS) released from host immune cells during the respiratory burst ( Wang et al, 2006 ).…”

“…It is widely known that KatA detoxifies hydrogen peroxide (H 2 O 2 ) and hypochlorite (OCl - ) ( Benoit and Maier, 2016 ). Additionally, we recently reported that KatA mediates vitronectin acquisition resulting in increased serum resistance ( Richter et al, 2016 ). Interestingly, despite the lack of a signal peptide, Helicobacter KatA is ubiquitous with various topology including the bacterial surface, the cytosol and periplasmic space.…”

Early steps in the evolution of vertical transmission revealed by a plant-bacterium symbiosis

“…ROS is often produced by plants in response to pathogen infection, but also plays an important role in plant signalling. Catalase has also been shown to be involved in host defence evasion by H. pylori by binding vitronectin [55]. Supporting this view, the sites under positive selection localize within an immune responsive domain at the C-terminal of the predicted protein, important for by T-cell interaction with H. pylori [56].…”

Host pathogen interactions in Helicobacter pylori related gastric cancer

“…The primary host immune response mechanisms, such as phagocytosis and natural killer (NK) cell activity, have been found to be downregulated by H. pylori LPS[17,18,39,40]. Adaptive immunity is also targeted by H. pylori compounds[1,15,41,42].…”