Distinct repeat motifs at the C-terminal region of CagA of Helicobacter pylori strains isolated from diseased patients and asymptomatic individuals in West Bengal, India

Santanu Chattopadhyay,Asish K Mukhopadhyay,T Ramamurthy,Douglas E Berg,Raghunath Chatterjee,Ronita De,G Balakrish Nair,Rajashree Patra,Jawed Alam,Abhijit Chowdhury

doi:10.1186/1757-4749-4-4

Abstract

BackgroundInfection with Helicobacter pylori strains that express CagA is associated with gastritis, peptic ulcer disease, and gastric adenocarcinoma. The biological function of CagA depends on tyrosine phosphorylation by a cellular kinase. The phosphate acceptor tyrosine moiety is present within the EPIYA motif at the C-terminal region of the protein. This region is highly polymorphic due to variations in the number of EPIYA motifs and the polymorphism found in spacer regions among EPIYA motifs. The aim of this study was to analyze the polymorphism at the C-terminal end of CagA and to evaluate its association with the clinical status of the host in West Bengal, India.ResultsSeventy-seven H. pylori strains isolated from patients with various clinical statuses were used to characterize the C-ternimal polymorphic region of CagA. Our analysis showed that there is no correlation between the previously described CagA types and various disease outcomes in Indian context. Further analyses of different CagA structures revealed that the repeat units in the spacer sequences within the EPIYA motifs are actually more discrete than the previously proposed models of CagA variants.ConclusionOur analyses suggest that EPIYA motifs as well as the spacer sequence units are present as distinct insertions and deletions, which possibly have arisen from extensive recombination events. Moreover, we have identified several new CagA types, which could not be typed by the existing systems and therefore, we have proposed a new typing system. We hypothesize that a cagA gene encoding higher number EPIYA motifs may perhaps have arisen from cagA genes that encode lesser EPIYA motifs by acquisition of DNA segments through recombination events.

Highlights

Infection with Helicobacter pylori strains that express CagA is associated with gastritis, peptic ulcer disease, and gastric adenocarcinoma
Prevalence of cagA types and clinical outcome Fifty-eight (31 of 40 duodenal ulcer patients (DU), 17 of 20 healthy volunteers (HV), 10 of 15 non-ulcer dyspeptics (NUD) and one from gastric adenocarcinoma patients (GC) of 77 H. pylori strains included in this study yielded a typical ~642 bp amplicon, designated as type A by Yamaoka et al (1998) (Table 1)
In Summary, we have identified seven CagA types and several of them are being reported for the first time including a CagA type, which carry a single EPIYA motif

Summary

Introduction

Infection with Helicobacter pylori strains that express CagA is associated with gastritis, peptic ulcer disease, and gastric adenocarcinoma. CagA multimerizes and undergoes tyrosine phosphorylation by Src family kinases to its tyrosine moiety, which resides in a repeat motif of five amino acids, glutamateproline-isoleusine-tyrosine-alanine (EPIYA), located at the C-terminal region of the protein [17,18,19,20]. Due to the intrinsic membrane tethering property of CagA the CagA-SHP-2 complex localizes to the plasma membrane of the host epithelium [21], leading to disregulation of the SHP-2 This event is necessary and sufficient to change the gastric epithelium to a transformed epithelium, which is characterized by altered cellular proliferation, migration and elongated cell morphology known as hummingbird phenotype [21,22]. The CagA disrupts the tight junctions and causes loss of apical-basolateral polarity in epithelial cells [23,24]

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