1)Urease:It 7. Therefore, further alkalisation of environmental

1)Urease:It is known that pH of human stomach is around 2.5. Since Helicobacter pylori is not an acidophile it is not possible for it survive in such harsh environment(.Eaton KA, Brooks CL, Morgan DR, Krakowka S. Essentialrole of urease in pathogenesis of gastritis induced by Helicobacter pylori in gnotobiotic piglets. Infect Immun 1991; 59:2470-2475 PMID: 2050411 )Its colonization in gut is highly favoured by urease enzyme which converts into ammonia and co2.ammonium carbonate which ultimately increases the pH of stomach and makes for the bacterium to survive in such low ph in th periplasm therefore contributing in proton motive force(. Stingl K, Altendorf K, Bakker EP. Acid survival of Helicobacterpylori: how does urease activity trigger cytoplasmic pH homeostasis? Trends Microbiol 2002; 10: 70-74 PMID:11827807 DOI: 10.1016/S0966-842X(01)02287-9)Another mechanism via which urease leads to periplasmic buffering can be with conversion of CO2 into bicarbonate by the action of periplasmic alpha carbonic anhydrase. (Marcus EA, Moshfegh AP, Sachs G, Scott DR. The periplasmic alpha-carbonic anhydrase activity of Helicobacter pyloriis essential for acid acclimation. J Bacteriol 2005; 187: 729-738PMID: 15629943 DOI: 10.1128/JB.187.2.729-738.2005).Presence of urease provides strong evidence for the persistence colonization of Helicobacter pylori in the human and perhaps can serve as a evidence that persistence of  helicobacter pylori is not found in any part of the human body since the normal pH of body is above 7. Therefore, further alkalisation of environmental pH can inhibit the growth of the Helicobacter pylori. (Factors that mediate colonization of the human stomach by Helicobacter pylori 2) Helical shape of Helicobacter pylori:Although it ,may not seem like an inessential factor but it plays a great deal in the pathological process of the bacterium in invasion of the mucuos membrane of the bacterium in the human gut. It provides a mechanistic screw-like movemnt helps in penetration in the epithelium. Apparently genes responsible for rhe bacterium morphology are as Ccrp89, Ccrp58, Ccrp1142 and Ccrp1143. any deletion or mutation may directly responsible for its colonisation. (Bansil R, Celli JP, Hardcastle JM, Turner BS. The Influenceof 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 strategy persists in Helicobater pylori:Cag A protein of bacterium has site that interacts with several host kinases at the site of phosphorylation site. The phosphorylation site consists of amino acid sequence called as EPIGYA.M. Stein, F. Bagnoli, R. Halenbeck, R. Rappuoli, W.J. Fantl, A. Covacci, c-Src/Lyn kinases activate Helicobacter pylori CagA through tyrosine phosphorylationof the EPIYA motifs, Mol. Microbiol. 43 (2002) 971e980 Role of src kinases and abl kinases in the persitenance with the Cag A protein in H.pylori: CagA is phosphorylated by Src kinases and can subsequently interfere with intracellular signalling pathways, leading to cell proliferation, cytoskeletal rearrangement, cell–cell adhesion loss, extracellular matrix remodelling and ß-catenin pathway activation. Based on geographical modification in the sequence of amino acid present in Cag A gene decides the variability on the pathogenicity of the gene present in the bacterium.Cag A has many other effects on epithelial cells when are bound which is it can agitate cell polarity and affects 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 the DNA found contains about 30 genes clusters; encode the gene resposible for cagA for glutamate racemase which is believed to be a cause of horizontal gene transfer. The pathogenicity of bacterium is highly dependent on the inflammatory response of the host cell which is dependent on the presence or absence of the pathogenicity island on the locus of DNA and severity of ots outcome. For instance cag+ can be seen to be assocated wiuth higher ratio of peptic ulcer to gastric ulcer rather than in the individual with negative or intermediate strains of the helicobacter pylori infections.  4)T4SS type 4 secretory system :Cag A protein is secreted via the Type IV secretion system (T4SS) into gastric epithelial cells, where it plays a pivotal role in the etiology of Helicobacter pylori associated gastric cancer. There are essentially 15 genes on the pathogenicity island required for the induction of T4SS, IL-8 and Cag A translocation or nucleotide-binding-oligomerization-domain(NOD1) signalling Key host–pathogen interactions for designing novel interventions against Helicobacter pylori. It is a multi subunit contact dependent secretion system which is encoded by Cag pathogenicity island and transfers to the host’s cell. The association between T4SS and Cag A is highly linked with the severity in the immunological responses that can often lead to gastric adenocarcinoma and peptic ulceration. (Life in the human stomach: persistence strategies of thebacterial pathogen Helicobacter pylori.)  5)Vac A toxin: Another secretory protein along side Cag A is Vac A. Vac A is a pore-forming toxin that alters the cell functionality and alters the mitochondria function, it permeates the plama membrane. Vac A genes are present in every strain of helicobacter pylori but also causes each strain possess different magnitude of pathological 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 ) situated pathogenic genes can result in programmed cell death, or act as an immunosuppressants meaning that they can check T-cells development. Helicobacter pylori has major antigenic determinants which are Vac A and GGT (?- glutamyl transpeptidase) both the factors intervene with that dendritic cells maturation as well as suppress activity of Treg( Tcell regulation) thereby developing toleration against Tcells.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 U S A. 2013; 110:3047–52. PubMed: 23382221  This helps Helicobacter pylori exceptional quality to resist the innate and adaptive immunity by escaping Th1 cells/ Th17 cells- polarized effector cells to adaption and influence of hosts system.Müller A, OertliM, Arnold IC (2011) H. pylori exploits and manipulates innate and adaptive immunecell signaling pathways to establish persistent infection. CellCommun Signal 9(1):25. 6)Motility:It has been seen that possession of flagella has been a key factor in the colonization and persistence in human gut. Presence of flagellar appaendages helps bacteria in motility confers endurance. Evidence from the mutant bacteria with absent flagella has affected its motility thus in its aftereffects in its host. Flagella drives it into the mucuos of host epithelium making it even easier for it to survive it in such atmosphere since Helicobacter pylori is not an acidophile it drive towards more hospitable environment that is towards mucous membrane of gastric epithelium and abundance of ammonium carbonate and neutral ph, amino acid and cholestrol via chemotactic propterties.(beyond the stomach). For full motility in the bacterium expression of two proetins are very crucial i.e., Fla A and Fla B regulated by Flh A. Any mutants with the absent in these proetin may lead to variablity in movement, infection and therefore, persistence. It has been found that functial of flagella is regulated by quoram sensing with the help of pheromones such as autoinducer-2 in response change in environment (.Rader BA, Campagna SR, Semmelhack MF, Bassler BL, Guillemin K. The quorum-sensing molecule autoinducer2 regulates motility and flagellar morphogenesis in Helicobacter pylori. J Bacteriol 2007; 189: 6109-6117 PMID:17586631 DOI: 10.1128/JB.00246-0745 ) (Shen F, Hobley L, Doherty N, Loh JT, Cover TL, Sockett RE, Hardie KR, Atherton JC. In Helicobacter pylori auto-inducer-2, but not LuxS/MccAB catalysed reverse transsulphuration,regulates motility through modulation of flagellar gene transcription. BMC Microbiol 2010; 10: 210 PMID: 20691071DOI: ????? Further studies revealed that mutant with hyper-motile phenotype from glycosylation of elevated in Fla A protein was seen to be increased activation of NF-?B hence 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 affects flagellin glycosylation to alter bacterial motility. Mol Microbiol2010; 78: 1130-1144 PMID: 21091500 DOI: 10.1111/j.1365-2958.2010.07393.x) 7)TNF-? All strains of helicobacter pylori are believed to contain TNF-? factor which is encoded by gene Tip? gene which along with various chemokines such as NF-?B.for new genes involved in the induction of TNF-a gene expression in gastric epithelial cells and identified a new gene encoding a TNF-? inducing protein, which we named ipa. ( M. Suganuma, M. Kurusu, K. Suzuki, et al., New tumor necrosis factor-ainducing protein released from Helicobacter pylori for gastric cancer progression, J. Cancer Res. Clin. Oncol. 131 (2005) 305–313. )TNF-? inducing Tip gene which in invasion in the host body induces higher inflammation of epithelium and increases the risk of gastric cancer. Tipgene is found on the Cag Pathogenicity Isalnd. It is unique since it as no resemblance to the other secretory proteins like urease, Cag A, Vac and it is independent of T4SS as well as of CagPAI. These findings indicate that colonization of helicobater was made effortless leading to entering into the hosts system and act upon. (M. Suganuma, K. Yamaguchi, Y. Ono, et al., TNF-a-inducing protein, acarcinogenic factor secreted from H. pylori, enters gastric cancer cells, Int. J.Cancer 123 (2008) 117–122) 8)Mandatory chemotaxis for Persistence:Rather then infecting helicobacter pylori persists in the anatomical niche of epithelial lumen of human gut. Mechanism are constantly evolving with increasing pathogenicity.( Helicobacter and Salmonella persistent infection strategiesDenise M. Monack) Chemotaxis by sensing little or ample change in pH are guiding factors in the movement of the bacterium and colonisation. Proteins like Che A, CheW, CheY and ChePep are responsible for chemotactic properties in the bacterium.Further studies also led to believe that mutant mice lack of ChePep protein could colonise into the lumen while when compared to the wildtype species ?ChePep had less of the virulence on the host to the ones carrying ChePep with enhanced sense of direction-routed infection.( Terry K, Williams SM, Connolly L, Ottemann KM. 2005.Chemotaxis plays multiple roles during Helicobacter pylori animal infection. Infect Immun 73: 803–811.)