The pathogenicity of Helicobacter pylori is dependent on factors including the environment and the host. Although selenium is closely related to pathogenicity as an environmental factor, the specific correlation between them remains unclear.

To investigate how selenium acts on virulence factors and reduces their toxicity.

H. pylori strains were induced by sodium selenite. The expression of cytotoxin-associated protein A (CagA) and vacuolating cytotoxin gene A (VacA) was determined by quantitative PCR and Western blotting. Transcriptomics was used to analyze CagA, CagM, CagE, Cag1, Cag3, and CagT. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction, and H. pylori colonization, inflammatory reactions, and the cell adhesion ability of H. pylori were assessed.

CagA and VacA expression was upregulated at first and then downregulated in the H. pylori strains after sodium selenite treatment. Their expression was significantly and steadily downregulated after the 5th cycle (10 d). Transcriptome analysis revealed that sodium selenite altered the levels affect H. pylori virulence factors such as CagA, CagM, CagE, Cag1, Cag3, and CagT. Of these factors, CagM and CagE expression was continuously downregulated and further downregulated after 2 h of induction with sodium selenite. Moreover, CagT expression was upregulated before the 3rd cycle (6 d) and significantly downregulated after the 5th cycle. Cag1 and Cag3 expression was upregulated and downregulated, respectively, but no significant change was observed by the 5th cycle. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction. The extent of H. pylori colonization in the stomach increased; however, sodium selenite also induced a mild inflammatory reaction in the gastric mucosa of H. pylori-infected mice, and the cell adhesion ability of H. pylori was significantly weakened.

These results demonstrate that H. pylori displayed virulence attenuation after the 10th d of sodium selenite treatment. Sodium selenite is a low toxicity compound with strong stability that can reduce the cell adhesion ability of H. pylori, thus mitigating the inflammatory damage to the gastric mucosa.

B-cell non-Hodgkin lymphoma (B-cell NHL) is the second commonest malignancy in the stomach. We determined the distribution of Helicobacter pylori outer membrane protein Q (HopQ) allelic type, cytotoxin-associated gene (cag)-pathogenicity activity island (cag-PAI) and vacuolation activating cytotoxin A (vacA) genes, respectively, in patients with B-cell NHL. We also compared them with their distribution in non-ulcer dyspepsia (NUD). H. pylori was cultured from gastric biopsy tissue obtained at endoscopy. Polymerase chain reaction was performed. Of 170 patients enrolled, 114 (63%) had NUD and 56 (37%) had B-cell NHL. HopQ type 1 was positive in 66 (58%) in NUD compared with 46 (82%) (P = 0·002) in B-cell NHL; HopQ type 2 was positive in 93 (82%) with NUD compared with 56 (100%) (P < 0·001) in B-cell NHL. Multiple HopQ types were present in 46 (40%) in NUD compared with 46 (82%) (P < 0·001) in B-cell NHL. CagA was positive in 48 (42%) in NUD vs. 50 (89%) (P < 0·001) in B-cell NHL; cagT was positive in 35 (31%) in NUD vs. 45 (80%) (P < 0·001) in B-cell NHL; left end of the cagA gene (LEC)1 was positive in 23 (20%) in NUD vs. 43 (77%) (P < 0·001) in B-cell NHL. VacAs1am1 positive in B-cell NHL in 48 (86%) (P < 0·001) vs. 50 (44%) in NUD, while s1am2 was positive in 20 (17%) in NUD vs. 46 (82%) (P < 0·001) in B-cell NHL. H. pylori strains with multiple HopQ allelic types, truncated cag-PAI evidenced by expression of cagA, cagT and cag LEC with virulent vacAs1 alleles are associated with B-cell NHL development.

We studied the prevalence of Helicobacter pylori virulence markers, e.g. cytotoxin associated gene (cagA), cagA promoter, vacuolating associated cytotoxin A (vacA) alleles induced by contact with epithelium (iceA type), and outer membrane protein Q (hopQ) in expatriates and compared them with those in local residents. Gastric biopsies were obtained at endoscopy for culture, histology and PCR for virulence marker and hopQ. Of 309 patients, 236 (76%) were males with a mean age of 45 years. A total of 102 patients were expatriates. hopQ type 1 was present in 98 (47%) local residents compared to 88 (86%) expatriates (P < 0·001), while hopQ type 2 was present in 176 (85%) local residents, compared to 60 (59%) expatriates (P < 0·001). H. pylori virulence marker cagA was positive in 97 (47%) local residents compared to 86 (84%) expatriates (P < 0·001) while cagA-P was positive in 72 (35%) local residents compared to 87 (85%) expatriates (P < 0·001). iceA type 1 was positive in 157 (76%) local residents compared to 45 (44%) expatriates (P < 0·001), while iceA type 2 was positive in 81 (39%) local residents compared to 86 (84%) expatriates (P < 0·001). Distribution of H. pylori cagA, cagA promoter, iceA and hopQ type in local residents and expatriates was different. H. pylori virulence markers were associated with severe pathology in expatriates.

Antibiotic resistance in Helicobacter pylori contributes to failure in eradicating the infection and is most often due to point and missense mutations in a few key genes.

The antibiotic susceptibility profiles of H. pylori isolates from 46 Pakistani patients were determined by Etest. Resistance and pathogenicity genes were amplified, and sequences were analyzed to determine the presence of mutations.

A high percentage of isolates (73.9%) were resistant to metronidazole (MTZ), with considerable resistance to clarithromycin (CLR; 47.8%) and amoxicillin (AML; 54.3%) also observed. Relatively few isolates were resistant to tetracycline (TET; 4.3%) or to ciprofloxacin (CIP; 13%). However, most isolates (n = 43) exhibited resistance to one or more antibiotics. MTZ-resistant isolates contained missense mutations in oxygen-independent NADPH nitroreductase (RdxA; 8 mutations found) and NADH flavin oxidoreductase (FrxA; 4 mutations found). In the 23S rRNA gene, responsible for CLR resistance, a new point mutation (A2181G) and 4 previously reported mutations were identified. Pathogenicity genes cagA, dupA, and vacA s1a/m1 were detected frequently in isolates which were also found to be resistant to MTZ, CLR, and AML. A high percentage of CagA and VacA seropositivity was also observed in these patients. Phylogenetic analysis of partial sequences showed uniform distribution of the 3' region of cagA throughout the tree.

We have identified H. pylori isolates in Pakistan which harbor pathogenicity genes and worrying antibiotic resistance profiles as a result of having acquired multiple point and missense mutations. H. pylori eradication regimens should therefore be reevaluated in this setting.

We aimed to assess the influence of Helicobacter pylori and its virulent factors, cytotoxin associated gene (cag) A and E, on portal hypertensive gastropathy (PHG) and the levels of interleukin (IL)-8, IL-10, and tumor necrosis factor-alpha (TNF-α).

The patients with cirrhosis underwent screening endoscopy and the lesions related to PHG were graded. Biopsies were obtained for histology, and polymerase chain reaction (PCR) of H. pylori 16S rRNA, cagA, cagE, and tissue cytokine levels was carried out. Absent or mild PHG was compared with moderate to severe PHG.

One hundred and forty patients with cirrhosis were studied; males numbered 92 and the mean age of the patients was 50.3 ± 12.0 years, H. pylori positivity in 87 (62.1%) patients was associated with male gender (P = 0.032), younger age (P = 0.029), hepatitis D etiology (P = 0.005), higher serum albumin (0.000), lower Child Pugh score (P = 0.001), and lower portal vein diameter (P = 0.001). There was no significant difference in the levels of TNF-α and IL-8. However, a decrease in the anti-inflammatory cytokine IL-10 was noted with moderate to severe gastropathy. Four H. pylori strains were positive for both cagA and cagE, while four were positive for cagA only. All the four patients with both virulent factors had mild gastropathy only.

The presence of H. pylori infection neither affected the severity of PHG nor augmented the IL-8 and TNF-α levels. There was a decline of virulent H. pylori strains and IL-10 levels in patients with advanced PHG.

Several genes including the cagA in the cag pathogenicity island (cag PAI) of Helicobacter pylori are thought to be associated with the gastroduodenal diseases and hence variation in the genetic structure of the cag PAI might be responsible for different clinical outcomes. Our study was undertaken to characterize the cag PAI of H. pylori strains from duodenal ulcer (DU) patients and asymptomatic or non-ulcer dyspepsia (NUD/AV) subjects from Kolkata, India. Strains isolated from 52 individuals (30DU and 22NUD/AV) were analyzed by PCR using 83 different primers for the entire cag PAI and also by dot-blot hybridization. Unlike H. pylori strains isolated from other parts of India, 82.6% of the strains used in this study had intact cag PAI, 9.6% had partially deleted cag PAI, and 7.7% of the strains lacked the entire cag PAI. Dot-blot hybridization yielded positive signals in 100% and 93.8% of PCR-negative strains for HP0522-523 and HP0532-HP0534 genes, respectively. An intact cagA promoter region was also detected in all cagA-positive strains. Furthermore, the expression of cagA mRNA was confirmed by RT-PCR for the representative strains from both DU and NUD/AV subjects indicating the active cagA promoter regions of these strains. A total of 66.7% of Kolkata strains produced a ∼390-bp shorter amplicon than the standard strain 26695 for the HP0527 gene, homologue of virB10. However, sequence analyses confirmed that the deletion did not alter the reading frame of the gene, and mRNA transcripts were detected by RT-PCR analysis. The strains isolated from DU and NUD/AV express CagA protein and possess a functional type IV secretion system, as revealed by Western blot analyses. Interestingly, no significant differences in cag PAI genetic structure were found between DU and NUD/AV individuals suggesting that other bacterial virulence factors, host susceptibility, and environmental determinants also influence the disease outcome at least in certain geographical locations.