Helicobacter pylori is responsible for the most commonly found infection in the world's population. It is the major risk factor for gastric cancer development. Numerous studies published over the last year provide new insights into the strategies employed by H. pylori to adapt to the extreme acidic conditions of the gastric environment, to establish persistent infection and to deregulate host functions, leading to gastric pathogenesis and cancer. In this review, we report recent data on the mechanisms involved in chemotaxis, on the essential role of nickel in acid resistance and gastric colonization, on the importance of adhesins and Hop proteins and on the role of CagPAI-components and CagA. Among the host functions, a special focus has been made on the escape from immune response, the ability of bacteria to induce genetic instability and modulate telomeres, the mechanism of autophagy and the deregulation of micro RNAs.

Purpose: Helicobacter pylori is a major cause of gastric carcinoma. To investigate a possible link between bacterial infection and genetic instability of the host genome, we examined the effect of H. pylori infection on known cellular repair pathways in vitro and in vivo. Moreover, various types of genetic instabilities in the nuclear and mitochondrial DNA (mtDNA) were examined. Experimental Design: We observed the effects of H. pylori infection on a gastric cell line (AGS), on C57BL/6 mice, and on individuals with chronic gastritis. In AGS cells, the effect of H. pylori infection on base excision repair and mismatch repair (MMR) was analyzed by reverse transcription-PCR, Western blot, and activity assays. In mice, MMR expression was analyzed by reverse transcription-PCR and the CA repeat instabilities were examined by Mutation Detection Enhancement gel electrophoresis. Mutation spectra in AGS cells and chronic gastritis tissue were determined by PCR, single-stranded conformation polymorphism, and sequencing. H. pylori vacA and cagA genotyping was determined by multiplex PCR and reverse hybridization. Results: Following H. pylori infection, the activity and expression of base excision repair and MMR are down-regulated both in vitro and in vivo. Moreover, H. pylori induces genomic instability in nuclear CA repeats in mice and in mtDNA of AGS cells and chronic gastritis tissue, and this effect in mtDNA is associated with bacterial virulence. Conclusions: Our results suggest that H. pylori impairs central DNA repair mechanisms, inducing a transient mutator phenotype, rendering gastric epithelial cells vulnerable to the accumulation of genetic instability and thus contributing to gastric carcinogenesis in infected individuals.

H. pylori drug-resistant strains and non-compliance to therapy are the major causes of H. pylori eradication failure. For some bacterial species it has been demonstrated that fatty acids have a growth inhibitory effect. Our main aim was to assess the ability of docosahexaenoic acid (DHA) to inhibit H. pylori growth both in vitro and in a mouse model. The effectiveness of standard therapy (ST) in combination with DHA on H. pylori eradication and recurrence prevention success was also investigated. The effects of DHA on H. pylori growth were analyzed in an in vitro dose-response study and n in vivo model. We analized the ability of H. pylori to colonize mice gastric mucosa following DHA, ST or a combination of both treatments. Our data demonstrate that DHA decreases H. pylori growth in vitro in a dose-dependent manner. Furthermore, DHA inhibits H. pylori gastric colonization in vivo as well as decreases mouse gastric mucosa inflammation. Addition of DHA to ST was also associated with lower H. pylori infection recurrence in the mouse model. In conclusion, DHA is an inhibitor of H. pylori growth and its ability to colonize mouse stomach. DHA treatment is also associated with a lower recurrence of H. pylori infection in combination with ST. These observations pave the way to consider DHA as an adjunct agent in H. pylori eradication treatment.

Helicobacter pylori is a human-specific pathogen which leads to gastric pathologies including gastric cancer. It is a highly unique bacterium considered as a carcinogenic agent. H. pylori remains a major human health problem, responsible for ~90% of the gastric cancer cases. Approximately four billion individuals have been detected for H. pylori infection worldwide in 2015. At the turn of the 21 st century, the prevalence of H. pylori has been declining in highly industrialized countries of the Western world, whereas prevalence has plateaued at a high level in developing and newly industrialized countries. However, the infection status remains high in immigrants coming from countries with high prevalence of H. pylori infection. H. pylori can be diagnosed by invasive and non-invasive methods. Urea breath test and stool antigens detection are among the most commonly used non-invasive ones. Although the way H. pylori is transmitted remains still unclear, the level of contamination is strongly dependent on the familial and environmental context, with a drastic impact of living conditions with poor hygiene and sanitation. However, familial socioeconomic status is the main risk factor for H. pylori infection among children. In addition, food and water source have a high impact on the prevalence of H. pylori infection worldwide. This chapter highlights the latest knowledge in the epidemiology of H. pylori infection, its diagnosis and critical risk factors responsible for its high prevalence in some populations and geographic areas.

The inactivation of the OGG1 DNA glycosylase in mouse leads to less severe inflammatory lesions and abolished the mutagenic effect at the gastric epithelial cells level, induced by the H. pylori infection. These data suggest for the OGG1deficiency a protective role against inflammation and genotoxicity associated to the H. pylori infection.

Helicobacter pylori induces chronic inflammation of the gastric mucosa, but only a proportion of infected individuals develop peptic ulcer disease or gastric carcinoma. Reasons underlying these observations include differences in bacterial pathogenicity as well as in host susceptibility. Numerous studies published in the last year provided new insight into H. pylori virulence factors, their interaction with the host and consequences in pathogenesis. These include the role of bacterial genetic diversity in host colonization and persistence, outer membrane proteins and modulation of adhesin expression, new aspects of VacA functions, and CagA and its phosphorylation‐dependent and ‐independent cellular effects. This article will also review the recent novel findings on the interactions of H. pylori with diverse host epithelial signaling pathways and events involved in the initiation of carcinogenesis, including genetic instability and dysregulation of DNA repair.

ObjectiveHelicobacter pylori (Hp) is a major risk factor for gastric cancer (GC). Hp promotes DNA damage and proteasomal degradation of p53, the guardian of genome stability. Hp reduces the expression of the transcription factor USF1 shown to stabilise p53 in response to genotoxic stress. We investigated whether Hp-mediated USF1 deregulation impacts p53-response and consequently genetic instability. We also explored in vivo the role of USF1 in gastric carcinogenesis.DesignHuman gastric epithelial cell lines were infected with Hp7.13, exposed or not to a DNA-damaging agent camptothecin (CPT), to mimic a genetic instability context. We quantified the expression of USF1, p53 and their target genes, we determined their subcellular localisation by immunofluorescence and examined USF1/p53 interaction. Usf1-/- and INS-GAS mice were used to strengthen the findings in vivo and patient data examined for clinical relevance.ResultsIn vivo we revealed the dominant role of USF1 in protecting gastric cells against Hp-induced carcinogenesis and its impact on p53 levels. In vitro, Hp delocalises USF1 into foci close to cell membranes. Hp prevents USF1/p53 nuclear built up and relocates these complexes in the cytoplasm, thereby impairing their transcriptional function. Hp also inhibits CPT-induced USF1/p53 nuclear complexes, exacerbating CPT-dependent DNA damaging effects.ConclusionOur data reveal that the depletion of USF1 and its de-localisation in the vicinity of cell membranes are essential events associated to the genotoxic activity of Hp infection, thus promoting gastric carcinogenesis. These findings are also of clinical relevance, supporting USF1 expression as a potential marker of GC susceptibility.

Epidemiological and experimental observations suggest that chronic microbial colonization can impact the immune control of other unrelated pathogens contracted in a concomitant or sequential manner. Possible interactions between Mycobacterium tuberculosis infection and persistence of other bacteria have scarcely been investigated. Here we demonstrated that natural colonization of the digestive tract with Helicobacter hepaticus in mice is concomitant with modification of the gut microbiota, subclinical inflammation, and drastic impairment of immune control of the growth of subsequently administered M. tuberculosis, which results in severe lung tissue injury. Our results provided insights upon the fact that this prior H. hepaticus colonization leads to failures in the mechanisms that could prevent the otherwise balanced cross-talk between M. tuberculosis and the immune system. Such disequilibrium ultimately leads to the inhibition of control of mycobacterial growth, outbreak of inflammation, and lung pathology. Among the dysregulated immune signatures, we noticed a correlation between the detrimental lung injury and the accumulation of activated T-lymphocytes. Our findings suggest that the impact of prior Helicobacter spp. colonization and subsequent M. tuberculosis parasitism might be greater than previously thought, which is a key point given that both species are among the most frequent invasive bacteria in human populations.