Helicobacter pylori is a spiral-shaped Gram-negative bacterium that colonizes the human stomach and can establish a long-term infection of the gastric mucosa, a condition that affects the relative risk of developing various clinical disorders of the upper gastrointestinal tract, such as chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma. H. pylori presents a high-level of genetic diversity, which can be an important factor in its adaptation to the host stomach and also for the clinical outcome of infection. There are important H. pylori virulence factors that, along with host characteristics and the external environment, have been associated with the different occurrences of diseases. This review is aimed to analyzing and summarizing the main of them and possible associations with the clinical outcome.

Helicobacter pylori (H. pylori) is an ancient microorganism that has co-evolved with humans for over 60000 years. This bacterium typically colonizes the human stomach and it is currently recognized as the most common infectious pathogen of the gastroduodenal tract. Although its chronic infection is associated with gastritis, peptic ulcer, dysplasia, neoplasia, MALT lymphoma and gastric adenocarcinoma, it has been suggested the possible association of H. pylori infection with several extragastric effects including hepatobiliary and pancreatic diseases. Since a microorganism resembling H. pylori was detected in samples from patients with hepatobiliary disorders, several reports have been discussed the possible role of bacteria in hepatic diseases as hepatocellular carcinoma, cirrhosis and hepatic encephalopathy, nonalcoholic fatty liver disease and fibrosis. Additionally, studies have reported the possible association between H. pylori infection and pancreatic diseases, especially because it has been suggested that this infection could change the pancreatic physiology. Some of them have related a possible association between the microorganism and pancreatic cancer. H. pylori infection has also been suggested to play a role in the acute and chronic pancreatitis pathogenesis, autoimmune pancreatitis, diabetes mellitus and metabolic syndrome. Considering that association of H. pylori to liver and pancreas diseases needs further clarification, our work offers a review about the results of some investigations related to the potential pathogenicity of H. pylori in these extragastric diseases.

An experimental murine model was used to verify the viability and pathogenicity of coccoid

SUMMARYHelicobacter pylori is a bacterium recognized as the major cause of peptic ulcer and chronic gastritis. Recently, a proteomebased approach was developed to investigate pathogenic factors related to H. pylori. In this preliminary study, H. pylori strains were isolated from gastric biopsies of patients with chronic gastritis and duodenal ulcers. A partial proteomic analysis of H. pylori strains was performed by bacterial lyses and proteins were separated by two-dimensional gel electrophoresis (2-DE). A comparative analysis was performed to verify a differential protein expression between these two 2-DE maps. These data should be useful to clarify the role of different proteins related to bacterial pathogenesis. This study will be completed using a larger number of samples and protein identification of H. pylori by MALDI-TOF mass spectrometry. KEYWORDS:Helicobacter pylori; Proteome; Bidimensional electrophoresis; Chronic gastritis; Peptic ulcers.Helicobacter pylori is a pathogenic bacterium associated with the etiopathogenesis of universally spread chronic gastritis, peptic ulcers, gastric adenocarcinoma and MALT-lymphoma, mainly in developing countries 1,5 . Several of its biological aspects have not been revealed yet, in spite of molecular studies about this bacterium. A strategy to improve these studies consists in analyzing the whole protein expressed by the organism in its microenvironment. This is defined as proteome and the methodology is based around the technique of two-dimensional electrophoresis, which is directed towards display of proteins expressed inside gels, followed by protein identification using Peptide Mass Fingerprinting mass spectrometry (MALDI-TOF-MS) 7,8,9 .Recently, some reports have described a comparison among 2-DE proteome maps of clinical isolates obtained from patients who had peptic ulcers and chronic gastritis. It has been found that the main proteins have a different expression in these 2-DE maps, including GroEL (a protein that increases urease enzyme activity) and SodF (an enzyme involved in free radical and hydrogen peroxide catabolism) 2,3 . In this work, we carried out a comparative analysis of 2-DE maps of H. pylori from Brazilian patients, in order to find molecular targets related to its pathogenic mechanism in clinical isolates derived from duodenal ulcers and gastritis.H. pylori strains were isolated from gastric mucosa biopsies of two patients who had not been previously treated, submitted to upper gastrointestinal endoscopy at Gastrocentro, UNICAMP. Bacterial isolation and protein extraction were performed according to our previous reports 6,8 .The samples were submitted to isoelectrofocusing (IEF) solubilized with 8M urea, 4% CHAPS, 70 mM DTT, ampholine linear pH gradient 4-7 (pH 4-7L) 1.5% and 0.001% bromophenol blue. At this stage, 64 μg of each protein sample were applied to polyacrylamide dried strips, pH gradient 4-7 L (immobilized pH gradient -IPG). The first dimension of 2-DE was performed on an Amersham Biosciences Electrophoresis System accumulating 96 ...

An experimental model for H. pylori infection was established by intragastrically challenging BALB/c mice with 1 ml (10 8 CFU/ml) of suspension for two consecutive days. Animals were divided into three groups. GA: mice inoculated with fresh bacteria; GB: mice inoculated with frozen bacteria, and GC: mice inoculated with brucella broth (control group). Animals were killed at 7, 14, 21, 28, 35 and 60 days pi and fragments of stomach and duodenum were collected, paraffin embedded and stained by hematoxylin-eosin and Giemsa. The results showed that challenged mice exhibited mild duodenitis and gastritis. In group GA, infiltration in the duodenum was lymphoplasmacytic until day 35; in group GB, it was lymphomonocytic for 60 days pi. In the stomach, H. pylori induced lymphomonocytic infiltration that was present from days 7 to 60 in group GA. In group GB, it was only present from days 14 to 35. In conclusion, our data suggested that freezing altered pathogenic properties of H. pylori and probably inhibited expression of bacterial antigens and consequently the establishment and maintenance of infection. Although the animals developed mild duodenitis and gastritis, the BALB/c mouse is not susceptible to developing peptic ulcers during H. pylori infection.