Recognition of Host Proteins by Helicobacter Cysteine-Rich Protein C

Abstract

Tetratricopeptide- and sel1-like repeat (SLR) proteins modulate various cellular activities, ranging from transcription regulation to cell-fate control. Helicobacter cysteine-rich proteins (Hcp) consist of several SLRs that are cross-linked by disulfide bridges and have been implicated in host/pathogen interactions. Using pull-down proteomics, several human proteins including Nek9, Hsp90, and Hsc71 have been identified as putative human interaction partners for HcpC. The interaction between the NimA-like protein kinase Nek9 and HcpC has been validated by ELISA and surface plasmon resonance. Recombinant Nek9 is recognized by HcpC with a dissociation constant in the lower micromolar range. This interaction is formed either directly between Nek9 and HcpC or via the formation of a complex with Hsc71. The HcpC homologue HcpA possesses no affinity for Nek9, suggesting that the reported interaction is rather specific for HcpC. These results are consistent with previous observations where Nek9 was targeted upon bacterial or viral invasion. However, further experiments will be required to show that the reported interactions also occur in vivo.

Microevolution of Virulence-Related Genes in Helicobacter pylori Familial Infection

“…The cagACTWY genes reside on the cag pathogenicity island [ 35 ]; vacA is known to cause vacuolation in host cells [ 36 ] and virB2 and comH are included in Type IV secretion systems, which are used for DNA import from the surrounding environment [ 37 ]. Cysteine-rich proteins [ 38 ] and HtrA protease [ 39 ] are involved in host interaction. The tnfα gene induces tumor necrosis factor alpha in the host [ 40 ] and gamma-glutamyltranspeptidase promotes pathogenesis [ 41 – 43 ].…”

Sequence Divergence and Conservation in Genomes of Helicobacter cetorum Strains from a Dolphin and a Whale

“…The three best known H. pylori SLR proteins are: HcpA, which may modulate immune responses to infection by stimulating the release of cytokines IFN-γ, TNF-α, IL-6, IL-10 and IL-12, and differentiation of Thp1 monocytes to macrophages [47]; HcpC, which facilitates GroEL chaperone and urease translocation to the bacterial surface, and stimulates H. pylori growth in mammalian cell cultures [48] and also interacts with eukaryotic protein kinase Nek9 (implicated in eukaryotic cell cycle regulation) [49]; and HP0519, which, as noted above, has undergone intense selection for amino acid change in particular human populations [23], [43]. Of these, only genes closely related to hcpC were found in H. cetorum genomes (genes HCD_08435 and HCW_08325; 86% and 79% protein level identity, respectively, to closest H. pylori hcpC homologs), although the C terminal 150 codons of HCD_03275 and HCW_00125 exhibit ∼32% protein level identity to corresponding regions of H. pylori HcpA.…”

Comprehensive mapping of the Helicobacter pylori NikR regulon provides new insights in bacterial nickel responses

“…Moreover, their expression associates with chronic atrophic gastritis38, and they have been shown to interact with host cells, inducing the production of IFNγ and other proinflammatory cytokines39. HcpC in particular fulfills different roles in the H. pylori virulence arsenal, ranging from immunoevasion to control of host invasion40. Evidence that hcpC is repressed by NikR and nickel, suggests that under nickel starvation the bacterium may boost its virulence, through one or more of the HcpC functions.…”