High incidence of antibiotic resistance amongst isolates of collected in Nottingham, UK, between 2001 and 2018.

is the leading cause of peptic ulcers and gastric cancer. The most common treatment regimens use combinations of two or three antibiotics and a proton pump inhibitor (PPI) to suppress stomach acid. The World Health Organization designated clarithromycin-resistant as a high priority pathogen for drug development, due to increasing antibiotic resistance globally.

The active form of Helicobacter pylori vacuolating cytotoxin induces decay-accelerating factor CD55 in association with intestinal metaplasia in the human gastric mucosa.

High-level expression of decay-accelerating factor, CD55, has previously been found in human gastric cancer (GC) and intestinal metaplasia (IM) tissues. Therapeutic effects of CD55 inhibition in cancer have been reported. However, the role of Helicobacter pylori infection and virulence factors in the induction of CD55 and its association with histological changes of the human gastric mucosa remain incompletely understood.

Helicobacter pylori-Mediated Protection from Allergy Is Associated with IL-10-Secreting Peripheral Blood Regulatory T Cells.

Helicobacter pylori infections are usually established in early childhood and continuously stimulate immunity, including T-helper 1 (Th1), Th17, and regulatory T-cell (Treg) responses, throughout life. Although known to be the major cause of peptic ulcer disease and gastric cancer, disease occurs in a minority of those who are infected. Recently, there has been much interest in beneficial effects arising from infection with this pathogen.

A role for the vacuolating cytotoxin, VacA, in colonization and Helicobacter pylori-induced metaplasia in the stomach.

Carriage of Helicobacter pylori strains producing more active (s1/i1) forms of VacA is strongly associated with gastric adenocarcinoma. To our knowledge, we are the first to determine effects of different polymorphic forms of VacA on inflammation and metaplasia in the mouse stomach. Bacteria producing the less active s2/i2 form of VacA colonized mice more efficiently than mutants null for VacA or producing more active forms of it, providing the first evidence of a positive role for the minimally active s2/i2 toxin.

Helicobacter pylori membrane vesicles stimulate innate pro- and anti-inflammatory responses and induce apoptosis in Jurkat T cells.

Persistent Helicobacter pylori infection induces chronic inflammation in the human gastric mucosa, which is associated with development of peptic ulceration, gastric atrophy, and gastric adenocarcinoma. It has been postulated that secretion of immunomodulatory molecules by H. pylori facilitates bacterial persistence, and membrane vesicles (MV), which have the potential to cross the gastric epithelial barrier, may mediate delivery of these molecules to host immune cells.

Clinical relevance of Helicobacter pylori cagA and vacA gene polymorphisms.

Background & Aims: The Helicobacter pylori gene cagA and s1 or m1 forms of vacA are more common in disease-associated strains. Recently, forms of cagA encoding multiple type C EPIYA segments (which increase phosphorylation-dependent CagA activity) and a new type i1 "intermediate region" polymorphism in vacA (which confers toxicity) have been described. We assessed the association of new and established cagA and vacA polymorphisms with disease.

A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer.

Background & Aims: Helicobacter pylori is the main cause of peptic ulceration and gastric adenocarcinoma. The vacuolating cytotoxin gene, vacA, is a major determinant of virulence. Two naturally polymorphic sites in vacA, the signal region and midregion, are well-characterized determinants of toxicity and markers of pathogenesis.

Paired cysteine residues are required for high levels of the Helicobacter pylori autotransporter VacA.

The Helicobacter pylori vacuolating cytotoxin VacA shares homology in its C-terminal domain with many autotransporter proteins, suggesting a similar mechanism of secretion. Like most autotransporters, VacA contains a single pair of cysteine residues located near the C-terminus of the passenger domain. This study aimed to investigate the role of these conserved cysteine residues.

Helicobacter pylori supernatants cause epithelial cytoskeletal disruption that is bacterial strain and epithelial cell line dependent but not toxin VacA dependent.

We show here that Helicobacter pylori broth culture supernatants disrupt the actin cytoskeleton of epithelial cell lines, leading to cell rounding and apoptosis through anoikis. We demonstrate that there are marked quantitative differences between strains and that there are different cell line sensitivities. By constructing VacA null isogenic mutants, we show that the effect is not due to the vacuolating cytotoxin.

Determinants of non-toxicity in the gastric pathogen Helicobacter pylori.

The Helicobacter pylori vacuolating cytotoxin gene, vacA, is naturally polymorphic, the two most diverse regions being the signal region (which can be type s1 or s2) and the mid region (m1 or m2). Previous work has shown which features of vacA make peptic ulcer and gastric cancer-associated type s1/m1 and s1/m2 strains toxic. vacA s2/m2 strains are associated with lower peptic ulcer and gastric cancer risk and are non-toxic.