Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2022.12.18.520940

A Genetic and Immunohistochemical Analysis of H. Pylori Phenotypes and p27 expression in Adenocarcinoma Patients in Jordan

Brown, B.·Mohammad, A. A. A.-R.·Shboul, Y.·Matalka, I.·A. Al-Sheboul, S.
View original source ↗Export metadata ↓

Abstract

Stomach (gastric) cancer is one of the most prevalent and deadly cancers worldwide and the vast majority of gastric cancers are adenocarcinomas. Based on prior research, there is an association between Helicobacter pylori (H. pylori) infection and the frequency of duodenal ulcer, distal gastric adenocarcinoma, mucosa-associated lymphoid tissue lymphoma, and antral gastritis. H. pylori virulence and toxicity factors have been identified to significantly influence the clinical outcomes of H. pylori infection and gastric adenocarcinoma. However, it is unclear exactly how different strains of H. pylori infection affect gastric adenocarcinoma. Current research suggests this involves tumor suppressor genes, like p27, but also H. Pylori toxic proteins. Therefore, we quantified known H. Pylori genotypes within adenocarcinoma patients to establish the prevalence of known toxins that include cytotoxin-associated gene A (cagA) and vacuolating cytotoxin A (vacA) within patients of variable diagnosis. This analysis used gastrectomy samples which were validated for DNA viability. The incidence of H. Pylori in adenocarcinoma patients in Jordan was established to be 54.5% positive (ureA gene) with cagA genotype occurrence at 57.1% but also vacA gene ratios 24.7%:22.1%: 14.3%:14.3%. (vacAs1:vacAs2: vacAm1:vacAm2). We found statistically significant evidence that p27 was dysregulated and suppressed within nearly all H. Pylori vacA genotypes but also that 24.6% of H. Pylori samples analyzed had a different bacterial genotype and curiously that p27 protein expression was retained in 12% of tested adenocarcinoma H. Pylori samples. This is suggestive that p27 could be used as a prognostic indicator but also that an unknown genotype could be contributing to the regulatory effects of p27 protein within this bacterial and cellular environment. Key ContributionIn Jordan, this is the first retrospective study to use validated viable gastrectomy tissue samples rather than tissue biopsies to characterize each of the currently defined H. pylori strains in patients with variable gastric cancer diagnosis whilst also comparing results with p27 expression within 8 years using these laboratory techniques. ConclusionsBased on these results, a reduction in p27 expression in H. pylori-infected men and women of all ages may be associated with the occurrence of gastric adenocarcinomas. Therefore, p27 may represent a key diagnostic marker and predictor of adenocarcinoma prognosis in such individuals and may find use for guiding subsequent treatment decisions.

Explore related subjects

microbiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Brown, B., Mohammad, A. A. A.-R., Shboul, Y., Matalka, I., A. Al-Sheboul, S.. 2022-12-19. A Genetic and Immunohistochemical Analysis of H. Pylori Phenotypes and p27 expression in Adenocarcinoma Patients in Jordan. https://doi.org/10.1101/2022.12.18.520940

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

A population-scale landscape of the subgingival microbiome reveals divergent routes to periodontal dysbiosis

Periodontitis is an archetypical mucosal inflammatory disease in which microbiome dysbiosis at the tooth-epithelial interface interacts with host genetic and behavioral risk factors to drive immune-mediated tissue destruction. Although subgingival microbiome compositional shifts are thought to parallel disease severity, microbiome variation at the population-level and its relationship to periodontal clinical phenotypes and disease-modifying factors remain poorly defined. Here, we use unsupervised manifold learning to map the compositional landscape of the subgingival microbiome in 1,355 adults spanning periodontal health to severe periodontitis. We identified eight latent microbiome states organized along a branching continuum from eubiosis to dysbiosis. An intermediate microbial configuration marked ecological destabilization and bifurcation into two distinct periodontitis-associated dysbiotic trajectories, distinguished by links to gingival inflammation and smoking. Although the microbiome trajectories broadly tracked periodontal destruction, a minority of individuals showed discordant microbiome-clinical phenotypes, with some individuals with periodontitis retaining otherwise eubiotic microbiomes enriched for low-abundance pathobionts, while some cases of health or mild disease had highly dysbiotic communities, suggesting distinct host susceptibility. Together, these findings define a population-scale ecological landscape of the subgingival microbiome, reveal divergent trajectories to periodontal dysbiosis, and highlight heterogeneity in the relationship between microbial community structure and clinical disease expression.

microbiology↗
bioRxiv2026

The iron-binding siderophore enterobactin is required for the response of multi-drug resistant Klebsiella pneumoniae to zinc limitation

To persist during infection Klebsiella pneumoniae must overcome nutrient iron and zinc limitation imposed by the host immune system through a process called nutritional immunity. Secreted small molecule siderophores are a major virulence determinant of Klebsiella pneumoniae pathogenesis and are presumed to overcome nutritional immunity by binding iron for bacterial acquisition. In this work, we set out to identify how a multi-drug resistant K. pneumoniae grows in zinc limited environments. Using unbiased transcriptomics, proteomics, and an arrayed transposon screen, we identified that synthesis and uptake of the siderophore enterobactin is required to allow for growth in low zinc conditions. Iron-specific chelators did not replicate this phenotype and addition of supplemental iron through heme in growth media could not complement severe growth defects of enterobactin mutant K. pneumoniae experiencing zinc limitation. Finally, zinc starvation induced enterobactin production independent of the canonical zinc uptake regulator (Zur) transcription factor suggesting an unidentified regulatory mechanism by which Gram-negative pathogens may respond to zinc stress. Together, these studies expand the role of enterobactin beyond iron regulation and highlight a previously unreported link between iron and zinc homeostasis in Klebsiella pneumoniae.

microbiology↗
bioRxiv2026

A microbiota-derived protease links phage susceptibility to host epithelial responses

Bacteriophages are major ecological drivers of gut microbial ecology, yet whether bacterial mechanisms that determine phage susceptibility have consequences for the mammalian host remains poorly understood. Here, we identify dipeptidyl peptidase 11 (Dpp11a), the predominant active serine protease of the prevalent gut commensal Phocaeicola vulgatus, as an unexpected bacterial defence factor. Dpp11a protects against environmental proteases and confers resistance to bacteriophage infection. Metatranscriptomic analyses further reveal increased expression of both dpp11a and P. vulgatus-associated phage transcripts in ulcerative colitis stool samples, indicating that both components of this interaction are transcriptionally active in disease-associated human microbiomes. Using the microfluidic gut-on-a-chip co-culture model HuMiX, we show that the absence of Dpp11 is accompanied by altered epithelial tight-junction remodelling during phage-bacterial infection. Together, our findings reveal that the consequences of bacterial phage defence can extend beyond phage-bacterium interactions to the mammalian epithelium.

microbiology↗