SUMMARY The discovery of Helicobacter pylori in 1982 was the starting point of a revolution concerning the concepts and management of gastroduodenal diseases. It is now well accepted that the most common stomach disease, peptic ulcer disease, is an infectious disease, and all consensus conferences agree that the causative agent, H. pylori, must be treated with antibiotics. Furthermore, the concept emerged that this bacterium could be the trigger of various malignant diseases of the stomach, and it is now a model for chronic bacterial infections causing cancer. Most of the many different techniques involved in diagnosis of H. pylori infection are performed in clinical microbiology laboratories. The aim of this article is to review the current status of these methods and their application, highlighting the important progress which has been made in the past decade. Both invasive and noninvasive techniques will be reviewed.

Helicobacter pylori has been associated with the development of two malignant diseases: gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Although the cag pathogenicity island, especially the cagA gene, has been linked with adenocarcinoma, few data concerning H. pylori pathogenic factors involved in low-grade gastric MALT lymphoma are available. The goal of this study was to analyze the prevalence of and correlation between genes coding for seven H. pylori virulence factors (cagA, cagE, vacA, iceA, babA, hopQ, and oipA) and two novel adhesins (sabA and hopZ) by comparing a collection of 43 H. pylori strains isolated from patients with low-grade gastric MALT lymphoma to 39 strains isolated from age-matched patients with gastritis only. Our results show that taken individually, none of the nine genes tested can be considered associated with MALT strains and allow us to conclude that MALT pathogenesis is not linked with more proinflammatory H. pylori strains. We demonstrated that in patients infected with strains harboring the iceA1 allele, sabA functional status, and hopZ "off" status, the odds of developing a MALT lymphoma were 10 times higher. However, the low prevalence of such strains (10 of 43 MALT strains) renders this triple association a low-sensitivity marker for MALT strains. Our data confirmed that H. pylori virulence factors are correlated with one another. If the involvement of H. pylori in MALT lymphoma is well established, the pathomechanism by which gastric lymphoma occurs remains to be identified.Helicobacter pylori infection is the essential etiological factor of type B chronic gastritis and peptic ulcer disease (29,35). It is also the first bacterium discovered to be involved in the development of malignant diseases: i.e., gastric carcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma (14,21,40). Following H. pylori colonization, inflammation occurs. Untreated gastritis may persist for years with different grades of severity. In some individuals, immunological stimulation induces lymphoid follicles in the gastric mucosa and provides the background for MALT lymphoma development (11), the polyclonal lymphoid hyperplasia evolving further toward a monoclonal lymphoid population (36). The reasons for this evolution, which is accompanied by genetic abnormalities, remain to be elucidated (33, 37). MALT lymphoma induction and growth are probably antigen driven, and it has been shown that H. pylori could be the trigger (18,23,24,26). Moreover, there is a demonstrated causal association between H. pylori infection and MALT-type lymphoma development, because it is possible to cure this cancer by eradicating H. pylori, suggesting that bacterial virulence factors exist and are associated with the disease development. H. pylori is the cause of approximately 80% of MALT lymphomas (8,57).Among the factors that may be linked to the outcome of infection, bacterial virulence factors such as cytotoxins and the cag pathogenicity island (PAI) have been extensively ...

Helicobacter pylori is a major human pathogen. Diagnosis of H. pylori infection and determination of its antibiotic susceptibility still mainly rely on culture and phenotypic drug susceptibility testing (DST) that is time-consuming and laborious. Whole genome sequencing (WGS) has recently emerged in medical microbiology as a diagnostic tool for reliable drug resistance prediction in bacterial pathogens. The aim of this study was to compare phenotypic DST results with the predictions based on the presence of genetic determinants identified in the H. pylori genome using WGS. Phenotypic resistance to clarithromycin, metronidazole, tetracycline, levofloxacin, and rifampicin was determined in 140 clinical H. pylori isolates by E-Test®, and the occurrence of certain single nucleotide polymorphisms (SNPs) in target genes was determined by WGS. Overall, there was a high congruence of >99% between phenotypic DST results for clarithromycin, levofloxacin, and rifampicin and SNPs identified in the 23S rRNA, gyrA, and rpoB gene. However, it was not possible to infer a resistance phenotype for metronidazole based on the occurrence of distinct SNPs in frxA and rdxA. All 140 H. pylori isolates analysed in this study were susceptible to tetracycline, which was in accordance with the absence of double or triple nucleotide substitutions in the 16S rRNA gene.

Peptic ulcer disease (PUD) occurs after a long-term Helicobacter pylori infection. However, the disease can develop earlier, and rare cases have been observed in children, suggesting that these H. pylori strains may be more virulent. We used suppressive subtractive hybridization for comparative genomics between H. pylori strains isolated from a 5-year-old child with duodenal ulcer and from a sex-and age-matched child with gastritis only. The prevalence of the 30 tester-specific subtracted sequences was determined on a collection of H. pylori strains from children (15 ulcers and 30 gastritis) and from adults (46 ulcers and 44 gastritis). Two of these sequences, jhp0562 (80.0% versus 33.3%, P ‫؍‬ 0.008) and jhp0870 (80.0% versus 36.7%, P ‫؍‬ 0.015), were highly associated with PUD in children and a third sequence, jhp0828, was less associated (40.0% versus 10.0%, P ‫؍‬ 0.048). Among adult strains, none of the 30 sequences was associated with PUD. However, both jhp0562 and jhp0870 were less prevalent in adenocarcinoma strains than in PUD strains from children and adults, the difference being statistically significant for jhp0870. In conclusion, two H. pylori genes were identified as being strongly associated with PUD in children, and their putative roles as an outer membrane protein for jhp0870 and in lipopolysaccharide biosynthesis for jhp0562, suggest that they may be novel virulence factors of H. pylori.Helicobacter pylori, a spiral-shaped gram-negative bacterium, can lead to various gastroduodenal diseases. A causal association has been established with chronic gastritis, peptic ulcer, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma (10). The mechanisms for such a clinically diverse profile are not totally clear but may include host and environmental factors, as well as bacterial virulence factors (7,20,23,47).In adult patients, severe gastroduodenal diseases such as duodenal ulcer, gastric adenocarcinoma, and MALT lymphoma occur after a long-term colonization (22, 47), while the onset of H. pylori infection is essentially during childhood (26). Indeed, the majority of H. pylori-infected children remain asymptomatic, except for a very small group which will develop peptic ulcer. Other factors such as nonsteroidal anti-inflammatory drug use, physiologic stress, and vascular insufficiency also play an important role beside H. pylori infection in the development of peptic ulcer in children (28). Moreover, colonization with H. pylori strains that are considered virulent in adults does not always correlate with the severity of endoscopic and histologic findings in children (24). These conflicting results may be due to the short-term infection, the association becoming possibly stronger as the duration of infection increases (53). Ulcers in children, in contrast to adults, appear shortly after H. pylori colonization, suggesting that differences exist between the ulcerogenic strains which infect children and adults and that strains associated with peptic ulcer in children may be m...

Gastric carcinomas (GC) are heterogeneous tumors, composed of a subpopulation of cluster of differentiation‐44 (CD44)+ tumorigenic and chemoresistant cancer stem cells (CSC). YAP1 and TAZ oncoproteins (Y/T) interact with TEA domain family member 1 (TEAD) transcription factors to promote cell survival and proliferation in multiple tissues. Their activity and role in GC remain unclear. This work aimed to analyze Y/T‐TEAD activity and molecular signature in gastric CSC, and to assess the effect of verteporfin, a Food and Drug Administration‐approved drug preventing Y/T‐TEAD interaction, on gastric CSC tumorigenic properties. Y/T‐TEAD molecular signature was investigated using bioinformatical (KmPlot database), transcriptomic and immunostaining analyses in patient‐derived GC and cell lines. Verteporfin effects on Y/T‐TEAD transcriptional activity, CSC proliferation and tumorigenic properties were evaluated using in vitro tumorsphere assays and mouse models of patient‐derived GC xenografts. High expressions of YAP1, TAZ, TEAD1, TEAD4 and their target genes were associated with low overall survival in nonmetastatic human GC patients (n = 444). This Y/T‐TEAD molecular signature was enriched in CD44+ patient‐derived GC cells and in cells resistant to conventional chemotherapy. Verteporfin treatment inhibited Y/T‐TEAD transcriptional activity, cell proliferation and CD44 expression, and decreased the pool of tumorsphere‐forming CD44+/aldehyde dehydrogenase (ALDH)high gastric CSC. Finally, verteporfin treatment inhibited GC tumor growth in vivo; the residual tumor cells exhibited reduced expressions of CD44 and ALDH1, and more importantly, they were unable to initiate new tumorspheres in vitro. All these data demonstrate that Y/T‐TEAD activity controls gastric CSC tumorigenic properties. The repositioning of verteporfin targeting YAP1/TAZ‐TEAD activity could be a promising CSC‐based strategy for the treatment of GC.

We describe isolates from human Campylobacter infection in the French population and the isolates' antimicrobial drug resistance patterns since 1986 and compare the trends with those of isolates from broiler chickens and pigs from 1999 to 2004. Among 5,685 human Campylobacter isolates, 76.2% were C. jejuni, 17.2% C. coli, and 5.0% C. fetus. Resistance to nalidixic acid increased from 8.2% in 1990 to 26.3% in 2004 (p<10-3), and resistance to ampicillin was high over time. Nalidixic acid resistance was greater for C. coli (21.3%) than for C. jejuni (14.9%, p<10-3). C. jejuni resistance to ciprofloxacin in broilers decreased from 31.7% in 2002 to 9.0% in 2004 (p = 0.02). The patterns of resistance to quinolones and fluoroquinolones were similar between 1999 and 2004 in human and broiler isolates for C. jejuni. These results suggest a potential benefit of a regulation policy limiting use of antimicrobial drugs in food animals.

This article summarizes the main findings concerning Helicobacter pylori associated with gastric MALT lymphoma (GML). Considered together, GML strains based on their virulence factor profile appear to be less virulent than those associated with peptic ulcers or gastric adenocarcinoma. A particular Lewis antigen profile has been identified in GML strains and could represent an alternative adaptive mechanism to escape the host immune response thereby allowing continuous antigenic stimulation of infiltrating lymphocytes.

The nucleotide sequence of the gyrA gene of Arcobacter butzleri, Arcobacter cryaerophilus, Arcobacter cibarius, and Arcobacter skirrowii was determined. The deduced GyrA proteins are closely related to those of Wolinella succinogenes and Helicobacter pullorum, whereas those of Campylobacter species showed less sequence identity. The phylogenetic analysis of GyrA sequences provides a result similar to 16S rRNA gene sequence phylogenetic analysis and allows the discrimination among A. butzleri species. In addition, a Thr-->Ile mutation at amino acid 85 in the quinolone resistance-determining region was associated with ciprofloxacin resistance for two A. butzleri and one A. cryaerophilus ciprofloxacin-resistant strains.