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

Abstract

BACKGROUND: Helicobacter pylori colonizes approximately half of the world’s human population. Its presence in the gastric mucosa is associated with an increased risk of gastric adenocarcinoma, gastric lymphoma, and peptic ulcer disease. In Brazil, the high prevalence of H. pylori infection is a serious health problem. H. pylori virulence factors are associated with an increased risk of serious gastrointestinal disorders. The cagA gene encodes a cytotoxin-A-associated antigen (CagA) that is involved in bacterial pathogenicity. H. pylori strains carrying the cag pathogenicity island (cag-PAI) are significantly associated with severe clinical outcomes and histopathological changes. OBJECTIVE: The present study aims to investigate the prevalence of the cagA gene among H. pylori isolates from patients with different gastric pathologies. Further, the study hopes to verify its association with clinical outcomes. In addition, phylogenetic analysis was performed on cagA-positive H. pylori strains from patients with severe and non-severe diseases. METHODS: Gastric specimens were collected through a biopsy from 117 patients with different esogastroduodenal diseases. DNA was extracted from these gastric specimens and the polymerase chain reaction was performed to amplify the gene fragments corresponding to the 16S ribosomal RNA and cagA genes using specific primers. The polymerase chain reaction products of selected samples positive for cagA were sequenced. The sequences were aligned with reference sequences from the National Center for Biotechnology Information (NCBI) (Bethesda/USA), and a phylogenetic tree was constructed. RESULTS: H. pylori was detected in 65.9% (77/117) of Brazilian patients with different gastroduodenal disorders. Overall, 80.5% (62/77) of the strains were cagA-positive. The ages of patients with cagA-positive strains (15 males and 47 females) ranged from 18 to 74 years. The lesions were categorized as non-severe and severe according to the endoscopic and histopathological reports the most prevalent non-severe esogastroduodenal lesion was gastritis 54/77 (70.12%), followed by esophagitis 12/77 (15.58%) and duodenitis 12/77 (15.58%). In contrast, the most prevalent severe lesions were atrophy 7/77 (9.09%), followed by metaplasia 3/77 (3.86%) and gastric adenocarcinoma 2/77 (2.59%). Phylogenetic analyses performed with the partial sequences of the cagA gene obtained from local strains were grouped in the same clade. No differences in phylogenetic distribution was detected between severe and non-severe diseases. CONCLUSION: The cagA gene is highly prevalent among H. pylori isolates from gastric lesions in Brazilian patients. The presence of the cagA gene was not considered a marker of the severity of esogastroduodenal lesions in the present study. This is the first study to investigate the phylogenetic population structure of H. pylori strains in a Brazilian capital, which may improve our understanding of the clinical outcome of H. pylori infection.

In silico prospective analysis of the medicinal plants activity on the CagA oncoprotein from Helicobacter pylori

“…They not only exhibit antimicrobial activity, as described for plants containing these compounds, but also have the ability to bind to and destabilize the interaction between CagA and epithelial cells. This interference could potentially prevent the initiation of changes leading to malignant transformation of gastric cells, such as the activation of PAR1/MARK kinases causing loss of cell polarization, and the inactivation of p53 resulting in uncontrolled and disordered cell proliferation[ 20 , 29 ].…”

“…The CagA is an oncoprotein, a virulence factor of H. pylori responsible for inducing genetic mutations and alterations in gastric cells[ 19 ]. This oncoprotein is encoded by the pathogenicity island (cag-PAI) and is transported into cells via a type 4 secretion system (T4SS)[ 20 ]. Inside cells, CagA attaches to the plasma membrane in two distinct ways: Through the interaction of basic amino acids, including those in the K-Xn-R-X-R binding motif located in the central region of CagA, or through the carboxy-terminus region.…”

“…Subsequently, CagA undergoes tyrosine phosphorylation on the EPIYA (Glu-Pro-Ile-Tyr-Ala) motif, which is present in multiple copies in the carboxy-terminus polymorphic region, by Src kinase members such as c-Src, Yes, Fyn, and Abl kinase[ 21 ]. Phosphorylated CagA interferes with cell signaling pathways, including the MAP kinase pathway, leading to mitogenic imbalance, induction of a pro-inflammatory state, cytoskeleton damage, and disruption of cell-cell junctions[ 20 , 22 , 23 ].…”

Pyloric Incompetence Associated with Helicobactor pylori Infection and Correlated to the Severity of Atrophic Gastritis

“…Patients diagnosed with open-type endoscopic atrophy have a higher risk of gastric cancer development than those diagnosed with closed-type [39][40][41]. Chronic H. pylori infection is a leading cause of gastric cancer [42,43]. The combination of bile reflux and H. pylori infection may cause progression to gastric cancer that may not be through the traditional process: inflammation-atrophy-metaplasia [44] Although the prevalence of H. pylori is decreasing, especially in developed countries with the expanded indication of H. Pylori eradication therapy, it is estimated that approximately 4.4 billion people are still infected with H. pylori worldwide [45].…”

Helicobacter Pylori Oipa Virulence Gene as a Molecular Marker of Severe Gastropathies

“…The other two samples were transported under refrigeration and stored at -20˚C at the Núcleo de Estudos da Helicobacter pylori (NEHP), located at the Federal University of Goiás. These samples were subjected to molecular analysis, in accordance with previous studies published by NEHP (19,20) .…”