| Helicobacter pylori(H. pylori) is the main pathogen of chronic gastritis, peptic ulcer, and it is closely related to gastric cancer and mucosa-associated lymphoid tumors (MALT). H. pylori were estimated to infect more than50%of global population and had been regarded as the class I carcinogen by the World Health Organization in1994. The cagPAI is a～37kb genomic island in H. pylori genome. The cagPAI genes encode a bacterial type IV secretion system (TFSS) as well as the effector protein, CagA. The TFSS translocates CagA into host cell to induse pathological changes. So cagPAI is closely related to H. pylori pathogenicity. Although cagPAI is a foreign genomic island acquired by homologous recombination, during coevolution with H. pylori for long time, its microdiversity is correlated with microdiversity within H. pylori housekeeping genes. Therefore, analysis of cagPAI sequence is representative for H. pylori evolution and pathogenicity research.In the present study,4cagPAI of Yunnan H. pylori were sequenced.64cagPAI sequences, including the4Yunnan cagPAI, of H, pylori strains from3regions in China and with different clinical background were studied on evolution and polymorphism. Base on the above research, we found cagA gene, especially for cagA-NT conserved region, is representative for cagPAI adaptive evolution of Chinese H. pylori strains. Geographical aggregation of Yunnan cagPAI sequences was related to the clusters of their cagA genes.33significant different point mutations between cagA sequences of Yunnan province and other regions were found and4of them were only in Yunnan strains.19significant different point mutations between cagPAI sequences of cancer related strains and gastritis related strains were found and10of them were positively correlated to cancer. Above discoveries provides a new marker gene for H. pylori’s adaptive evolution study and new reference sites for disease outcome prediction of H. pylori infection.Current eradication therapies for H. pylori include triple eradication therapy consisting of one proton pump inhibitor (PPI) and two antibiotics, bismuth-contain quadruple therapy, sequential therapy and concomitant therapy. Antibiotic resistance status, especially for double or multiple drugs resistance, of H. pylori were serious. The unacceptable performance of legacy triple therapy was in parallel with a progressive increase in the prevalence of antimicrobial resistance. Tailored treatment is the most effective therapy for H. pylori eradication in high resistant population. For make specific therapeutic regimen, comprehensive epidemiologic surveillances of H. pylori resistances to antibiotics in different regions are required.In the second part of this study, susceptibility testing data of6antibiotics on17,731H. pylori strains were collected from eight areas of two provinces in coastal southeast China from2010to2012was analyzed. Local resistance status of first and second line antibiotics, multiple resistance and relevent factors were described and discussed. In the present study, we found The prevalence of H. pylori resistance to clarithromycin, metronidazole, levofloxacin and multiple antibiotics in coastal southeast China is high. Choice of therapy should be individualized based on a susceptibility test in local high resistance populations. Different antibiotic resistance level among different areas and populations and correlation between different H. pylori antibiotic resistance are attributing to patient’s economic condition and choice of drugs. We suggest employ the three low resistance antibiotics:amoxicillin, gentamicin, and furazolidone, as the fist-line and rescue choice for H. pylori infection treatment.In this research, we studied on the sequence characteristic of disease-related genes and treatment of H. pylori, which made better understanding of correlation among H. pylori evolution, genetic polymorphism, geographic aggregation and pathogenicity. And it also discussed how to make specific therapeutic regimen to cope with high resistance situation of H. pylori. The present study will be helpful for knowing H. pylori deeply, and will be meaningful on guidincg following research and H. pylori treatment. |
PDF Full Text Request