Pathogenesis of Helicobacter pylori infection

Abstract

In this review, we highlight progress in the last year in characterizing known virulence factors like flagella and the Cag type IV secretion system with sophisticated structural and biochemical approaches to yield new insight on the assembly and functions of these critical virulence determinants. Several aspects of Helicobacter pylori physiology were newly explored this year and evaluated for their functions during stomach colonization, including a fascinating role for the essential protease HtrA in allowing access of H. pylori to the basolateral side of the gastric epithelium through cleavage of the tight junction protein E-cadherin to facilitate CagA delivery. Molecular biology tools standard in model bacteria, including regulated gene expression during animal infection and fluorescent reporter gene fusions, were newly applied to H. pylori to explore functions for urease beyond initial colonization and establish high salt consumption as a mediator of gene expression changes. New sequencing technologies enabled validation of long postulated roles for DNA methylation in regulating H. pylori gene expression. On the cell biology side, elegant work using lineage tracing in the murine model and organoid primary cell culture systems has provided new insights into how H. pylori manipulates gastric tissue functions, locally and at a distance, to promote its survival in the stomach and induce pathologic changes. Finally, new work has bolstered the case for genomic variation as an important mechanism to generate phenotypic diversity during changing environmental conditions in the context of diet manipulation in animal infection models and during human experimental infection after vaccination.

High expression of Helicobacter pylori VapD in both the intracellular environment and biopsies from gastric patients with severity

“…However, the VapD expression levels detected in all the biopsies were high enough to believe that an important number of vapD-positive H. pylori strains were colonizing both gastric antrum and corpus in all patients. The impact of H. pylori virulence factors on the development of gastroduodenal diseases [3,23,24] is well documented. CagA is an oncoprotein, which is injected into host cells via a pilus structure called type IV secretion system (T4SS) encoded for cag-PAI [3,23,24].…”

“…The impact of H. pylori virulence factors on the development of gastroduodenal diseases [3,23,24] is well documented. CagA is an oncoprotein, which is injected into host cells via a pilus structure called type IV secretion system (T4SS) encoded for cag-PAI [3,23,24]. VacA is a cytotoxin that induces vacuole formation in eukaryotic cells.…”

“…H. pylori colonization induces an inflammatory response; however, the microorganism uses mechanisms to protect itself from the immune response and from being eliminated from the gastric mucosa, thereby allowing long-time persistence. Various virulence factors are associated with gastric pathologies, such as a vacuolizing cytotoxin (VacA), the cytotoxin-associated gene A (CagA), the cag pathogenicity island and outer-membrane proteins (OMPLA, BabA, OipA) [3]. However, the prevalence of these virulence factors is diverse among H. pylori strains and between isolates from different geographic areas and ethnic groups [4].…”

The eradication of Helicobacter pylori restores rather than disturbs the gastrointestinal microbiota in asymptomatic young adults

“…Helicobacter pylori (H pylori) infects over half of the world's population and causes a series of gastric diseases including superficial gastritis, chronic atrophic gastritis, and peptic ulcers. 1 Moreover, long-term H pylori infection can lead to gastric malignancies, which have been demonstrated in both human and animal models; thus, H pylori has been recognized as a class I carcinogen by the International Agency for Research on Cancer. 2 Recently, a number of clinical studies have demonstrated that the earlier H pylori eradication therapy is given, especially prior to the development of precancerous lesions, the more effective it will be in reducing the risk of gastric cancer.…”

Nutraceuticals as modulators of gut microbiota: Role in therapy

“…Two well‐defined clinical entities provide a vivid illustration of disrupted microbiome‐host interactions: Clostridioides difficile‐ associated disease (CDAD) and Helicobacter pylori infection. The former serves as a dramatic reminder of the consequences of iatrogenic disruptions of a microbiome that, when intact, serves to protect us against pathogens (Britton & Young, ; Schäffler & Breitrück, ), and the latter exemplifies how host genome, bacterial properties and the immune response conspire to produce various disease phenotypes (Noto & Peek, ; Thorell, Lehours, & Vale, ; Waskito, Salama, & Yamaoka, ).…”