# A Review on Flavonoids as Anti-_Helicobacter pylori_ Agents
## 3 Results
### Review on H. pylori Infection and Treatment
#### 3.1.3 Genome and Markers  
_H. pylori_ was first isolated in 1983 from a stomach biopsy and had the genome sequenced in 1997. In 1999, the bacteria had a comparative analysis using the genotypes 26,695 and 199. This comparative analysis helped to understand its evolution and the identification of its unique genes [35; 36; 37; 38]. Considering its importance as a class I mutagenic agent, the number of genotypes sequenced has been increasing using different patients. These sequences are being deposited at NCBI (National Centre for Biotechnology Information) and PATRIC (Pathosystem Resource Integration Centre) [1; 19; 39]. _H. pylori_ has also been sequenced from Iceman--a 5300-year-old European mummy [40]. The genome comparative analysis showed a high level of genomic diversity due to point mutations, recombination, slipped-strand mispairing, and inter-genomic recombination. All this information is essential for the identification of potential targets that can be used for developing new drugs using biotechnological tools [1]. These analyses show two important factors: a) bacterial genotype is important for disease severity, and b) host polymorphism in IL-18 and CYP2C19. These genes are important for PPI metabolization and might be associated with the risk of cancer development [1; 41]. Furthermore, the genome analysis showed that _H. pylori_ has a pan-genome (defined as the entire gene repertoire in each species). According to the genotypes analysed, the comparative analysis proposes that the core genome might have only 244 genes, and the virulent factors can be classified as part of the dispensable genome [42]. All this information helps to identify the potential targets for drug development and new treatment protocols. In addition, [PERSON] et al. observed that samples from infected children and adults exhibited altered expression of _GATA-5_ and _trefoil factor_ 1 (_iff_) [43]. In their study, _GATA-5_ methylation was associated with infection, suggesting that epigenetic silencing in the gastric mucosa at earlier stages may contribute to cancer progression. They also detected an increase in the expression of miRNA-146a and miRNA-155, which may serve as indicators of chronic infection. It was verified that _hom_A and _hom_B's expression was modified in children with severe gastritis [3]. They proposed that these two genes may act synergistically and that they can be used as markers for the severity of the disease. Working with protein glycosylation, it was verified that proteins associated with adhesion glycosylation might be potential targets for _H. pylori_ infection treatment [44]. _H. pylori_ metabolism and host infection were analysed, and many genes/proteins that are important for bacteria metabolism, infection, and colonisation were identified [45]. A point raised by them, corroborated by other papers, is that these sequences can be used as markers for the development of new drugs and protocols for treatment (Table 1) [1; 45; 46]. One sequence is the urease gene, which is found exclusively in bacteria and is vital for their survival in the stomach's acidic environment. Additionally, the chemotaxis system directs the bacteria toward the protective mucus layer of the gastric mucosa [45; 47; 48]. Urease protein is formed by two subunits, UreA and UreB. For its activity, nickel ions (Ni) with a nickel-responsive regulator (NikR) must be present to uptake Ni. Then, it is transported to the cytoplasm, where the urease is present, by nickel-cobalt transporter (NixA). The outer membrane proteins (OMPs) are important for colonisation in the bacteria's adhesion to gastric cells. The _oip_A gene encodes the OipA outer membrane protein, and _the bab_A gene codifies the BabA protein, where both proteins are important for adhesion [1; 45].