**6. Pathogenesis of infection**

#### **6.1** *H. pylori***-associated pathogenesis**

Chronic active gastritis is the principal disease after *H. pylori* colonization. In all *H. pylori*-positive subjects this syndrome can be found. Various different factors such as colonizing stress characteristics, host physiology, immune response, diet, and development rate depend on the intragastric distribution and intensity of the chronic inflammatory process. Many of the complications of this chronic inflammation include *H. pylori*-induced ulcers, gastric cancer and lymphoma; in particular, ulcerative and gastric cancers arise in these people and in the areas of the most serious inflammation. Therefore, recognizing these factors is important in order to consider *H. pylori's* role in the etiology of the upper gastrointestinal disorder [42].

*H. pylori* colonizes the membrane in the stomach antrum of the gastric epithelia. *H. pylori* adhere to the stomach epithelia is a prime and significant step towards colonization of gastric mucosa and gastritis [78].

In duodenum, *H. pylori* only infects gastric mucosa and gastric metaplasia [79]. In comparison, on intestinal epithelium *H. pylori* is never seen. Dunn *et al*., stated in vitro, that *H. pylori* was more effective than human intestine (Int-407) cells, and sac cells with yolk bags, on human gastric epithelial cells [80]*.* Similarly, the adherence rate of *H. pylori* to gastric cell lines (KatoIII, MKN45) was shown to be significantly higher than that to Int-407 cells. These results indicate that *H. pylori* has specific binding activity to human gastric epithelial cells [81].

In a logarithmic point, *H. pylori* has strong nourishment with a spiral morphology. But spiral to coccoid conversion may be inducted by alkaline pH, rise in temperature, antibiotic therapy, aerobics or anaerobics, or prolonged incubation. The type of coccoid *H. pylori* is known as viable but not cultivable. *H. pylori* coccoid bind to both the stomach epithelial MKN45 cells and the spiral form. Although it is unknown whether the coccoid form has any role in the infection pathogenesis., Cole *et al."* The type of coccoid has been reported to bind badly to gastric epithelial cells. In contrast to spiral shape the form induces a short interleukin 8 (IL-8) chain. The coccoid shape, by comparison, was more frequent than the spiral of *H. pylori* induces cellular changes of pedestal formation [82].

#### **6.2 Gastric environment at the site of infection**

The human stomach has a medium luminal pH, with elevations until around pH 4 during meals due to nutrient buffering, when set to natural physiological acid secretion [83]. *H. pylori* originally occupied a more neutral niche at the gastric region with gastric acidity defense offered by the secretion of bicarbonate from epithelial cells and mucus. Studies with glass microelectrodes indicated a pH gradient in the stomach mucus and an epithelial pH virtually neutral [84]. The measuring technique may have delayed these studies as open tip microelectrodes may have stopped proton diffusion. Later microelectrode experiments using a similar method of calculation in mice found that all obstacles to the proton diffusion were eliminated and acidic pH was indicated in the bacterial niche [85]. Fluorescent dyeing tests in the anesthetic mice's externalized stomachs showed an acidic gastral pH surface regardless of the mucus layer [86]. The pH of the gastric surface is a

#### *Pathophysiology of* H. pylori *DOI: http://dx.doi.org/10.5772/intechopen.96763*

combination between the regulation of acid and alkaline secretion at a certain stage instead of the trapping of mucus-layer buffers or protons [87].

Analysis of *H. pylori* transcriptome provides additional evidence of acidic pH on gastric surfaces. Several in Vitro experiments have reported improvements in acidic pH expression of the gene using varying duration and conditions of incubation [87–89]. The unifying finding of these research studies is that there are a variety of genes that alter expression depending on environmental pH and indicate adaptation in order to permit gastric colonization.

The well-documented movements of *H. pylori* from its usual gastric niche to the fundus in human or gerbil acid inhibitory Therapy are proof that the bacteria need to remain in a particular pH setting [90–92]. The *H. pylori* transcriptome has been studied in the gerbil's stomach to correlate with in vitro pH changes [93]. Gerbil is a suitable model system since the gastric pH profile of *H. pylori* and its advanced sequelae are close to the ones found in humans [94–96]. The pattern of *H. pylori* gene changes in the gerbil stomach were comparable to gene changes seen in vitro at acidic pH, providing additional evidence for an acidic environment at the site of infection [97].

### **6.3 Attaching and effacement by adherence of** *H. pylori*

Attaching and effacement is characterized by microvilli effacement, actin rearrangement and pedestal formation following bacterial adhesion to cells as described for enteropathogenic *Escherichia coli* (EPEC) [7]. The attachment and effacement of *H. pylori* in the gastric cells have been documented [97].

The tyrosine Phosphorylation of two host cell proteins (145 kDa and 105 kDa) has been shown to be inducted after *H. pylori* binding to gastric pathologic cells. Although it is hypothesized that tyrosine Phosphoryphorylation of host cell proteins is implicated in pathogenesis of gastric diseases related to *H. pylori* infection However, other researchers found that an attachment of *H. pylori* does not contribute to pedestal formation or actin rearrangement [98].

#### **6.4 Adhesin of** *H. pylori* **and its receptor**

*H. pylori* adhesively adheres to a receptor on the gastric cell surface by its adhesives. The adhesins and their receivers have been recorded in several respects. As the adhesion of *H. pylori* to cells is not entirely hindered by the human antibody to an adhesin, adherence by the use of many adhesins and their receptors is known to be the outcome*.*

#### **6.5 HpaA (Sialyllactose-Binding Adhesin)**

Evans *et al.* to purified 20 kDa protein as an adhesin of *H. pylori* recognizing N-acetylneuraminyllactose, and cloned its gene, *hpaA.* The protein HpaA functions as hemagglutinin and aggregates the fibrillary structure together. HpaA is stated to be a lipoprotein intracellular and the inactivation of the HpaA did not affect *H. pylori's* adherence to gastric cells. Consequently, the value of HpaA as *H. pylori* adhesin is contentious [99].

#### **6.6 Adhesin recognizing phosphatidylethanolaurine**

Specific binding of *H. pylori* to a glycerophospholipid species in the antrum of the human stomach was reported. The thin-layer chromatogram overlay technique showed this species to be a type of phosphatidylethanolamine. Since the exoenzyme from *Pseudomonas aeruginosa* displays similar binding specificity, the binding of *H. pylori* to its lipid receptor was expected to be induced by an exoenzyme S-like adhesive [100].

#### **6.7 BabA protein recognizing Lewisb antigen**

The lewis antigens (Lewis, Lewisb, Lewisx, and LewisY) are one of the bloodgroup antigens that is flucosylated and expressed in human epithelics and erythrocytes. Lewis antigen that recognizes non-secretory blood groups (O) has been reported to be mediating adhesion of *H. pylori* to human gastric epithelial cells. Preferential relation between *H. pylori* and Lewisb antigen suggests that certain patients are more vulnerable to the development of peptic ulcers [101].

#### **6.8 Adhesin recognizing extracellular matrix components**

Many researchers have reported that *H. pylori* has been bound to different extracellular matrix components such as vitronectin, heparin sulfate, collagen, fibronectin, lactoferrin, plasminogen and laminin. There are about 20 Specific attachment of *H. pylori* to extracellular matrix components promotes bacterial colonization [102].

#### **6.9 Induction of secretion of various cytokines from gastric cells**

In vivo, *H. pylori* gastric infection induces several cytokines, including IL–l beta, IL–6, IL-7 and alpha tumor necrosis, to develop mucous membranes. IL-8 particularly consists of a small peptide (chemokine), secreted by a range of cell types, which helps to attract and activate neutrophils as a powerful inflammatory mediator. IL-8 development stimulation in gastric epithelial cells was recorded by *H. pylori.* The positive CagA strains displayed a significant increase in IL-8 relative to cag negative strains. Transposon inactivation of several genes in *cagA* pathogenicity island (PAl) showed that various genes *(cagB)* C) *D) E)* G) *H,* ~ *L) A1)* were responsible for the induction of IL-8 from gastric epithelial cells [29]. Recently, Li et al., [30] reported that multiple genes encoding HP052l, 0525, 0527, 0528 and 0529 ORF in the left half of the *cag* PAl of *H. pylori* are required for tyrosine-kinase dependent transcription of IL-8 in gastric epithelial cells. In addition, Yamaguchi et al., [31] reported the induction of IL-8 by HSP60 of *H. pylori* from gastric epithelial KatoIII cells [103].
