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

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.

Analysis of the intactness of Helicobacter pylori cag pathogenicity island in Iranian strains by a new PCR-based strategy and its relationship with virulence genotypes and EPIYA motifs

“…However, our results differed from Southeast Asian countries (Sahara et al, 2012), where both Western and Eastern types of CagA were present. In contrast to some Asian countries such as Korea (Choi et al, 2007), Vietnam (Uchida et al, 2009) and India (Chattopadhyay et al, 2012) where the Eastern type CagA (EPIYA-D) is dominant, we did not observe any EPIYA-D motifs in our strains. Similar to previous reports (Karlsson et al, 2012;Monstein et al, 2010;Sgouras et al, 2009;Vaziri et al, 2013), some of our H. pylori-positive patients (9.6%) showed different CagA EPIYA motifs, which indicated the presence of two H. pylori strains in the same patient.…”

The VacA and the CagA of Helicobacter pylori : Two Multitasking Proteins of a Multitasking Bacterium

“…The presence of East Asian specific sequence (ESS) in CagA primary structure is hypothesized to be the reason for occurrence of more gastric cancer cases in Japan due to stronger intracellular response than the Western specific (WSS) CagA sequence [49,50] . Between any two EPIYA motifs presence of several discrete motifs (possibly due to recombination events at the 3' end of the cagA) were also reported [50][51][52][53] . Based on PCR, the cagA 3' end region that encodes the EPIYA motif and adjacent repeat units can be typed and different nomenclatures were proposed [50][51][52] .…”

“…Between any two EPIYA motifs presence of several discrete motifs (possibly due to recombination events at the 3' end of the cagA) were also reported [50][51][52][53] . Based on PCR, the cagA 3' end region that encodes the EPIYA motif and adjacent repeat units can be typed and different nomenclatures were proposed [50][51][52] .…”

“…The cagA 3' end encodes a stretch of five amino acids motif, EPIYA, and the tyrosine (Y) residue within this motif can become phosphorylated [49] . The number of the EPIYA motifs (usually 3-5 for most strains, but 1 and 2 EPIYA motifs were also reported) and the amino acid sequences among the EPIYA motifs vary between the Western and East Asian H. pylori strains [18,49,51] . The presence of East Asian specific sequence (ESS) in CagA primary structure is hypothesized to be the reason for occurrence of more gastric cancer cases in Japan due to stronger intracellular response than the Western specific (WSS) CagA sequence [49,50] .…”

A letter to the editor comment on: five-year monitoring of considerable changes in tyrosine phosphorylation motifs of the Helicobacter pylori cagA gene in Iran

“…This controversy results from the method that Kargar et al used in their study; they only used PCR method for EPIYA typing which considerably reduced the impact of their study. Based on the well known EPIYA typing protocol (Hatakeyama 2004;Chattopadhyay et al 2012) the only acceptable methods for CagA EPIYA typing is PCR and sequencing.…”