Functional Divergence ofHelicobacter pyloriRelated to Early Gastric Cancer

Abstract

Helicobacter pylori is an extra macro- and microdiverse bacterial species, but where and when diversity arises is not well-understood. To test whether a new environment accelerates H. pylori genetic changes for quick adaptation, we have examined the genetic and phenotypic changes in H. pylori obtained from different locations of the stomach from patients with early gastric cancer (ECG) or chronic gastritis (CG). Macroarray analysis did not detect differences in genetic content among all of the isolates obtained from different locations within the same stomach of patients with EGC or CG. The extent and types of functional diversity of H. pylori isolates were characterized by 2-D difference gel electrophoresis (2D DIGE). Our analysis revealed 32 differentially expressed proteins in H. pylori related to EGC and 14 differentially expressed proteins in H. pylori related to CG. Most of the differentially expressed proteins belong to the antioxidant protein group (SodB, KatA, AphC/TsaA, TrxA, Pfr), tricarbon acid cycle proteins (Idh, FrdA, FrdB, FldA, AcnB) and heat shock proteins (GroEL and ClpB). We conclude that H. pylori protein expression variability is mostly associated with microorganism adaptation to morphologically different parts of the stomach, which has histological features and morphological changes due to pathological processes; gene loss or acquisition is not involved in the adaptation process.

Differential Proteomics of Helicobacter pylori Associated with Autoimmune Atrophic Gastritis

“…An additional property in interaction with the extracellular matrix of infected host cells was also proposed by Backert et al (71). High levels of EF-Tu expression in HP isolates from GC patients have been reported (32,62). In our work, the lowest content of EF-Tu in the HP proteome associated with AAG was accompanied by a low content of another protein involved in protein biosynthesis: the ribosome-recycling or -releasing factor, responsible for the release of ribosomes from mRNA at the termination of translation (72).…”

“…With the exception of two works (31,32), which were based on a DIGE approach, our study is the first to analyze the HP protein isolated from patients with different gastric diseases by twodimensional DIGE approaches. Moreover, to our knowledge, at present, there is a lack of comparative proteomics information among maps of clinical HP strains isolated from patients affected by AAG and those of clinical HP strains isolated from patients affected by DU or GC.…”

“…The protein was reported in HP proteome by several works (31,43,60), as well as in the proteomes of some gastric disease-associated HP strains (32). The important role of flagellin A in both bacterial motility and virulence is well documented (61).…”

“…HP catalase acts synergistically together with other decomposing proteins to detoxify the cell from aggressive oxygen metabolites, thus preventing the misfolding or unfolding of proteins under long-term stress conditions. For these reasons, HP catalase is included among the HP virulence factors, and it has been reported as an important enzyme in different HP-related disorders such as gastritis, GC and DU (24,32,55). Probably the overexpressed catalase found in AAG compared with GC in our series is associated with either a more accentuated oxidative stress occurring during AAG state with respect to the GC ones, or, alternatively, an environmental selection of bacteria with a higher capability to counteract oxidative stress by enzyme overexpression.…”

Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks

“…There are a number of resources in the world that allow reconstruction of such associative gene networks, for example, MetaCore [27], Ingenuity [28] and ANDSystem [29,30]. In particular, using the developed by us ANDSystem tool, the following studies were performed: analysis of proteomic data on Helicobacter pylori infection [31]; analysis of the urine proteomic profile in control and under the influence of space flight factors [32]; analysis of tissue-specific gene knockout effect and the search for potential drug targets [33]; analysis of hepatitis C virus life cycle gene networks [34]; analysis of comorbid relations of bronchial asthma and tuberculosis [35], preeclampsia, diabetes and obesity [36], glaucoma [37]; search for novel candidate genes of susceptibility to tuberculosis [38].…”