Biological evidence of the relationship between Helicobacter pylori and associated extragastric diseases. Zendehdel Abolfazl,Roham Maryam Journal of cellular biochemistry BACKGROUND:Gram-negative bacterium, Helicobacter pylori is notorious for various pathologies like peptic ulcers, gastritis, functional dyspepsia, and various cancers. METHODS:Systemic effects of its toxins have led scientists' attention toward the extragastric pathologies associated with it. To date, it has been shown to have an effect on almost all the systems in the human body. RESULTS:Various studies have been conducted to obtain the relation between H. pylori infection, and other diseases. CONCLUSION:In this review, we aim to discuss the extragastric diseases associated with H. pylori and the biological factors that relate them to it. 10.1002/jcb.28681

Lipoprotein Processing and Sorting in Helicobacter pylori. mBio Our current understanding of lipoprotein synthesis and localization in Gram-negative bacteria is based primarily on studies of Newly synthesized prolipoproteins undergo posttranslational modifications catalyzed by three essential enzymes (Lgt, LspA, and Lnt). The mature lipoproteins are then sorted to the inner or outer membrane via the Lol system (LolABCDE). Recent studies suggested that this paradigm may not be universally applicable among different classes of proteobacteria. In this study, we conducted a systematic analysis of lipoprotein processing and sorting in , a member of the that colonizes the human stomach. We show that , , and homologs can complement conditionally lethal mutant strains in which expression of these genes is conditionally regulated. Mutagenesis studies and analyses of conditionally lethal mutant strains indicate that and are essential for growth but is dispensable. and the single (or ) homolog are also essential genes. We then explored the role of lipoproteins in Cag type IV secretion system (Cag T4SS) activity. Comparative analysis of the putative VirB7 homolog CagT in wild-type and mutant strains indicates that CagT undergoes amino-terminal modifications consistent with lipidation, and we show that CagT lipidation is essential for CagT stability and Cag T4SS function. This work demonstrates that lipoprotein synthesis and localization in diverge from the canonical pathways and that lipidation of a T4SS component is necessary for Cag T4SS activity. Bacterial lipoproteins have diverse roles in multiple aspects of bacterial physiology, antimicrobial resistance, and pathogenesis. Dedicated pathways direct the posttranslational lipidation and localization of lipoproteins, but there is considerable variation in these pathways among the proteobacteria. In this study, we characterized the proteins responsible for lipoprotein synthesis and localization in , a member of the that contributes to stomach cancer pathogenesis. We also provide evidence suggesting that lipidation of CagT, a component of the Cag T4SS, is required for delivery of the CagA oncoprotein into human gastric cells. Overall, these results constitute the first systematic analysis of lipoprotein production and localization pathways and reveal how these processes in differ from corresponding pathways in model proteobacteria. 10.1128/mBio.00911-20

The effect of altered pH growth conditions on the production, composition, and proteomes of Helicobacter pylori outer membrane vesicles. Proteomics Gram-negative bacteria release outer membrane vesicles (OMVs) that contain cargo derived from their parent bacteria. Helicobacter pylori is a Gram-negative human pathogen that produces urease to increase the pH of the surrounding environment to facilitate colonization of the gastric mucosa. However, the effect of acidic growth conditions on the production and composition of H. pylori OMVs is unknown. In this study, we examined the production, composition, and proteome of H. pylori OMVs produced during acidic and neutral pH growth conditions. H. pylori growth in acidic conditions reduced the quantity and size of OMVs produced. Additionally, OMVs produced during acidic growth conditions had increased protein, DNA, and RNA cargo compared to OMVs produced during neutral conditions. Proteomic analysis comparing the proteomes of OMVs to their parent bacteria demonstrated significant differences in the enrichment of beta-lactamases and outer membrane proteins between bacteria and OMVs, supporting that differing growth conditions impacts OMV composition. We also identified differences in the enrichment of proteins between OMVs produced during different pH growth conditions. Overall, our findings reveal that growth of H. pylori at different pH levels is a factor that alters OMV proteomes, which may affect their subsequent functions. 10.1002/pmic.202300269

(Re)-definition of the holo- and apo-Fur direct regulons of Helicobacter pylori. Journal of molecular biology Iron homeostasis is a critical process for living organisms because this metal is an essential co-factor for fundamental biochemical activities, like energy production and detoxification, albeit its excess quickly leads to cell intoxication. The protein Fur (ferric uptake regulator) controls iron homeostasis in bacteria by switching from its apo- to holo-form as a function of the cytoplasmic level of ferrous ions, thereby modulating gene expression. The Helicobacter pylori HpFur protein has the rare ability to operate as a transcriptional commutator; apo- and holo-HpFur function as two different repressors with distinct DNA binding recognition properties for specific sets of target genes. Although the regulation of apo- and holo-HpFur in this bacterium has been extensively investigated, we propose a genome-wide redefinition of holo-HpFur direct regulon in H. pylori by integration of RNA-seq and ChIP-seq data, and a large extension of the apo-HpFur direct regulon. We show that in response to iron availability, new coding sequences, non-coding RNAs, toxin-antitoxin systems, and transcripts within open reading frames are directly regulated by apo- or holo-HpFur. These new targets and the more thorough validation and deeper characterization of those already known provide a complete and updated picture of the direct regulons of this two-faced transcriptional regulator. 10.1016/j.jmb.2024.168573

Biological properties and pathogenicity factors of Helicobacter pylori. Isaeva Guzel S,Fagoonee Sharmila Minerva gastroenterologica e dietologica The unexpected discovery of Helicobacter pylori (H. pylori) has revolutionised the history of microbiology as well as of gastroenterology in the last 30 years, with an invaluable benefit for millions of persons worldwide. The confirmation that this Gram-negative spiral bacterium could live in the stomach has rendered out-of-date the concept of inhospitality of micro-organisms in the gastric environment, after a long history of unheard reports on the presence of spiral bacteria in the stomach. The pathogenicity of H. pylori depends on its ability to colonize as well as the capability to survive in the harsh gastric environment. This is possible by a coevolution between the pathogen itself and the host. Any perturbation of this equilibrium disrupts the host-pathogen interaction, promoting the pathological effects. H. pylori has a wide range of pathogenicity factors, in particular cytotoxins, enzymes of aggression, and factors providing protection against human defense systems. The most well-characterized cytotoxins contributing to epithelial cell damage are the vacuolating cytotoxin A (VacA) and the cytotoxin-associated gene A (CagA). Only detailed knowledge of the microbiology and genomics of H. pylori infection will allow a vaccine to be produced. Today, we know that H. pylori induces strong humoral and cellular immune responses, but these are incapable of eliminating the bacterium, raising doubts about the possibility of developing an effective vaccine easily. This review highlights microbiological findings concerning H. pylori infection, focusing on colonization, survival and pathogenicity. 10.23736/S1121-421X.18.02479-0