In this review, we mainly focus on the persistent colonization of Helicobacter pylori in the human intestine. In recent times we have come across some new strategies used by this bacterium which may be the cause of prolonged existence in humans or of evolution with another bacterium to optimize its existence. The balance between the bacterium and the responding human cells played an important role in the persistence of the bacterium in its colonization or confers the risk of organ dysfunction leading to more serious diseases such as gastric adenocarcinoma, lymphoma, gastric peptic ulcer and many others. A recently discovered new factor is the secreted protease HtrA (high temperature requirement A), which has been shown to cleave the ectodomain of E-cadherin, an important cell adhesion protein and tumor suppressor, with crucial consequences for the disorder of the epithelial barrier functions Some of the factors essential for the survival of the bacterium Helicobacter pylori in the human intestine and which lead to a number of serious diseases are: Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get Original Essay1) Urease: The pH of the human stomach is known to be around 2.5. Since Helicobacter pylori is not an acidophilus, it is not possible for it to survive in such a hostile environment(.Eaton KA, Brooks CL, Morgan DR, Krakowka S. Essential role of urease in pathogenesis of gastritis induced by Helicobacter pylori in gnotobiotic piglets. Infect Immun 1991; 59:2470-2475 [PMID: 2050411] ) Its colonization in the intestine is highly favored by the enzyme urease which converts to ammonia and ammonium co2.carbonate which ultimately increases the pH of the stomach and allows the bacterium to survive. in such a low pH in the periplasm, therefore, contributing to the proton motive force(. Stingl K, Altendorf K, Bakker EP. Acid survival of Helicobacter pylori: how do urease activity trigger cytoplasmic pH homeostasis? Trends Microbiol 2002; 10: 70- 74 [PMID:11827807 DOI: 10.1016/S0966-842X(01)02287-9]) Another mechanism by which urease leads to periplasmic buffering may be the conversion of CO2 to bicarbonate through the action of alpha carbonic anhydrase periplasmic. (Marcus EA, Moshfegh AP, Sachs G, Scott DR. Periplasmic alpha-carbonic anhydrase activity of Helicobacter pylori is essential for acid acclimation. J Bacteriol 2005; 187: 729-738[PMID: 15629943 DOI: 10.1128 /JB.187.2.729-738.2005]). The presence of urease provides strong evidence for the persistence of Helicobacter pylori colonization in humans and perhaps can serve as evidence that the persistence of Helicobacter pylori is not found anywhere in the human body since the normal pH of the body is above 7. Therefore, further alkalinization of the environmental pH can inhibit the growth of Helicobacter pylori. (Factors that mediate colonization of the human stomach by Helicobacter pylori2) Helicoidal shape of Helicobacter pylori: Although it may not seem like an inessential factor, it plays a lot in the pathological process of the bacterium in the invasion of the mucosa of the human stomach bacterium into the human intestine . It provides a mechanistic screw motion that aids in penetration into the epithelium. Apparently the genes responsible for the morphology of the bacterium are Ccrp89, Ccrp58, Ccrp1142 and Ccrp1143. any deletion or mutation could be directly responsible for its colonization. (Bansal R, Celli JP, Hardcastle JM, Turner BS. The Influence of Mucus Microstructure and Rheology in Helicobacter pylori Infection. Front Immunol 2013; 4: 310 [PMID: 24133493 DOI:10.3389/fimmu.2013.00310])3) Cag A mediated The strategy persists in Helicobacterpylori:Cag A bacterial protein has a site that interacts with several host kinases at the site of the phosphorylation site. The phosphorylation site consists of a sequence of amino acids called EPIGYA.M. Stein, F. Bagnoli, R. Halenbeck, R. Rappuoli, WJ Fantl, A. Covacci, c-Src/Lyn kinases activate Helicobacter pylori CagA through tyrosine phosphorylation of EPIYA motifs, Mol. Microbiol. 43 (2002) 971e980 Role of Src kinases and all kinases in persistence with Cag A protein in H.pylori: CagA is phosphorylated by Src kinases and can subsequently interfere with intracellular signaling pathways, leading to cell proliferation, rearrangement cytoskeletal, to loss of cell adhesion, remodeling of the extracellular matrix and activation of the ß-catenin pathway. Based on the geographical change in the sequence of amino acids present in the Cag A gene, the variability in the pathogenicity of the gene present in the bacterium decides. Cag A has many other effects on epithelial cells when they are bound, i.e. it can agitate cell polarity and influence multiple host cell pathways. (Amieva MR, El-Omar EM. 2008. Host-bacterial interactions in Helicobacter pylori infection. Gastroenterology 134:306–323) Cag PAI (Cag Pathogenicity Island) is a locus on DNA found to contain approximately 30 gene clusters ; encode the cagA gene responsible for glutamate racemase which is thought to be a cause of horizontal gene transfer. The pathogenicity of the bacterium is strongly dependent on the inflammatory response of the host cell which depends on the presence or absence of the pathogenicity island in the DNA locus and the severity of its outcome. For example, it can be observed that cag+ is associated with the higher ratio between peptic ulcer and gastric ulcer rather than in subjects with negative or intermediate strains of Helicobacter pylori infections.4) T4SS type 4 secretory system: the Cag A protein is secreted via the type IV secretion system (T4SS) in gastric epithelial cells, where it plays a critical role in the etiology of Helicobacter pylori-associated gastric cancer. There are essentially 15 genes on the pathogenicity island required for induction of T4SS, IL-8, and Cag A translocation or nucleotide-binding oligomerization domain (NOD1) signaling Key host-pathogen interactions for designing new interventions against Helicobacter pylori. It is a contact-dependent multisubunit secretion system that is encoded by the Cag pathogenicity island and transfers to the host cell. The association between T4SS and Cag A is strongly linked to the severity of immunological responses which can often lead to gastric adenocarcinoma and peptic ulcer. (Life in the human stomach: persistence strategies of the bacterial pathogen Helicobacter pylori.)5) VacA toxin: Another secretory protein along with Cag A is Vac A. VacA is a pore-forming toxin that alters cellular function and alters function of mitochondria, permeates the plasma membrane. The Vac A genes are present in every strain of Helicobacter pylori, but cause each strain to possess a different extent of the disease process. (Kim IJ, Blanke SR. Remodeling the host Environment: modulation of the gastric epithelium by the Helicobacter pylori vacuolating toxin (VacA ). Front Cell Infect Microbiol. 2012; 2:37 [PubMed: 22919629]) located pathogenic genes can cause programmed cell death or act as immunosuppressants, which means they can control the development of T cells. Helicobacter pylori has important antigenic determinants which are VacA and GGT (?-glutamyl transpeptidase). Both factors intervene in the maturation of dendritic cells and suppress Treg activity (regulation of T cells), thus developing tolerance against T cells.Oertli M, Noben M, Engler DB, et al. Helicobacter pylori gamma-glutamyl transpeptidase and vacuolating cytotoxin promote gastric persistence and immune tolerance. Proc Natl Acad Sci US A. 2013; 110:3047–52. [PubMed: 23382221]This helps exceptional Helicobacter pylori resist innate and adaptive immunity by escaping Th1 cells/Th17 cells - effector cells polarized to adapt and influence the host system. Müller A, OertliM, Arnold IC (2011) H. pylori exploits and manipulates innate and adaptive immune cell signaling pathways to establish persistent infection. CellCommun Signal 9(1):25.6) Motility: Possession of flagella was found to be a key factor in colonization and persistence in the human gut. The presence of flagellar appendages helps the bacteria in motility and confers resistance. Tests of the mutant bacteria with absent flagella affected its motility and therefore its side effects in its host. The flagella push it into the mucous membranes of the host epithelium, making survival in this atmosphere even easier since Helicobacter pylori is not an acidophilus, they push it towards a more hospitable environment, that is, towards the mucosa of the gastric epithelium and the abundance of ammonium carbonate and neutral pH, amino acids and cholesterol through chemotactic properties (beyond the stomach). For full motility in the bacterium, the expression of two proteins is very crucial, namely Fla A and FlaB regulated by Flh A. Any mutant absent in this protein can lead to variability in movement, infection and therefore persistence. It has been found that the functioning of flagella is regulated by quorum sensing with the help of pheromones such as autoinducer-2 in response to changing environment (.Rader BA, Campagna SR, Semmelhack MF, Bassler BL, Guillemin K. The quorum-sensing molecule autoinducer2 regulates flagellar motility and morphogenesis in Helicobacter pylori 2007 189: 6109-6117 [PMID:17586631 DOI: 10.1128/JB.00246-07]45 (Shen F, Hobley L, Doherty N, Loh JT, Cover TL)., Sockett RE, Hardie KR, Atherton JC In Helicobacter pylori autoinducer-2, but not LuxS/McCabe-catalyzed reverse transsulfuration, regulates motility through modulation of flagellar gene transcription ??? revealed that the mutant with hypermotile phenotype resulting from glycosylation of Fla A protein increased NF-?B activation, thus increased infection (Asakura H, Churin Y, Bauer B, Boettcher JP, Bar-. *tfeld S, Hashii N, Kawasaki N, Mollenkopf HJ, Jungblut PR, Brinkmann V, Meyer TF. Helicobacter pylori HP0518 influences flagellin glycosylation to alter bacterial motility. Mol Microbiol2010; 78: 1130-1144 [PMID: 21091500 DOI: 10.1111/j.1365-2958.2010.07393.x])7) TNF-a It is believed that all Helicobacter pylori strains contain the TNF-a factor encoded by the Tipa gene which together to various chemokines such as NF-?B.for new genes involved in the induction of TNF-a gene expression in gastric epithelial cells and we identified a new gene encoding a protein that induces TNF-a, which we called IPA . (M. Suganuma, M. Kurusu, K. Suzuki, et al., Novel tumor necrosis factor-induced protein released by Helicobacter pylori for gastric cancer progression, J. Cancer Res. Clin. Oncol. 131 (2005) 305–313. )TNF-a Tip gene that induces invasion into the host body induces increased inflammation of the epithelium and increases the risk of gastric cancer. The main gene is found on Pathogenicity Island Cag. It is unique as it bears no similarity to other secretory proteins such as urease, Cag A, Vac and is independent of T4SS and CagPAI. These results indicate that Helicobacter colonization occurred effortlessly enough to enter the host system and act accordingly. (M., 73: 803–811.)