CagL polymorphisms D58/K59 are predominant in Helicobacter pylori strains isolated from Mexican patients with chronic gastritis

Abstract

Background: Helicobacter pylori is a Gram-negative bacterium that colonizes the gastric mucosa in humans. One of the main virulence factors of H. pylori is the cag pathogenicity island (cagPAI), which encodes a type 4-secretion system (T4SS) and the cytotoxin CagA. Translocation of CagA through the T4SS triggers host-signaling pathways. One of the T4SS proteins is CagL, which is necessary for CagA translocation. CagL is a 26-kDa protein that contains a hypervariable motif, which spans residues 58 to 62. Several polymorphisms in this region have been associated with different disease outcomes, e.g. in Mexico, N58 is associated with a higher risk of gastric cancer. The aim of this work is to analyze the sequence of the hypervariable motif (residues 58 to 62) of clinical isolates from Mexican patients with chronic gastritis, and to correlate these polymorphisms with the vacA genotype. Results: Of the 164 biopsies analyzed, only 30.5% (50/164) were positive for H. pylori. Thirty-six of the 50 clinical isolates (72%) were cagA positive, and 40 (80%) had the most virulent vacA genotype (s1/m1). Of the cagA positive strains, 94.4% were vacA s1/m1. All the cagA + strains contained the cagL gene. The most prevalent sequence in the polymorphic region (residues 58-62) was DKMGE (75.8%, 25/33), followed by NKMGQ and NEIGQ (6.1%, 2/33), and DEIGQ, NKMGE, DKIGE, and DKIGK (3%, 1/33). Regarding polymorphisms in positions 58 and 59, the most common were D58/K59 (81.8%, 27/33), followed by N58/K59 (9.1%, 3/33), and D58/E59 (3%, 1/33). Only two isolates (6.1%) contained residues N58/E59, which correspond to those found in H. pylori strain ATCC 26695. 92.6% of the clinical isolates having polymorphism D58/K59 had the genotype vacA s1/m1, considered to be the most virulent, while 7.4% had the genotypes vacA s1/m2 and s2/m2. Conclusions: In Mexican patients, CagL polymorphisms D58, K59, M60, E62, K122, and I134 are more common in patients with chronic gastritis.

Genetic polymorphisms in the cag pathogenicity island of Helicobacter pylori and risk of stomach cancer and high‐grade premalignant gastric lesions

“…More recent sequencing studies have identified a number of variants in this gene. The other cagL variant associated with GC in our study, on residue 134, has been reported with variable results in other studies in Latin America 34,36,37 ; although this variant has not been detected in East Asian strains 33,35 . Thus, although the data from these Western strains are inconclusive in terms of its association with GC, this cagL variant is likely to represent a Western strain‐specific marker.…”

“…To date, Hp genotyping on biopsy specimens has been almost limited to CagA EPIYA motif patterns 32 . There are more recent studies based on sequencing technology, reporting associations between specific Hp genetic variants and clinical phenotypes 33‐37 . However, these sequencing studies have been performed on a limited number of samples and with Hp strains isolated from the patients.…”

Helicobacter pylori Virulence Factors Exploiting Gastric Colonization and its Pathogenicity

“…This RGD-dependent binding of CagL to integrins was also shown to trigger intracellular signaling pathways inducing cell pro-inflammatory responses that are CagA translocation-independent [46,137,138]. Recent studies found an association of novel CagL variants with chronic gastritis and peptic ulcer disease (PUD) development [139,140]. Particular polymorphisms upstream of the RGD motif at amino acid residues 58–62, called the CagL hypervariable motif (CagLHM), are correlated with severe disease progression in a geographically-dependent manner [141,142].…”

HELICOBACTER PYLORI cagA VIRULENCE GENE AND SEVERE ESOGASTRODUODENAL DISEASES: IS THERE AN ASSOCIATION?

“…These included Chile (15.2%) and Malaysia (43.0%) (24,33) . The different rate of detection of the cagA gene can possibly be attributed to the genetic polymorphism, characteristics of different H. pylori strains, as well as the different rates of prevalence of infection in these countries (34) .…”