Analysis of Helicobacter pylori infections in Africa, bacterial virulence factors but lack of pathology

革兰氏阴性细菌病原体幽门螺杆菌（Helicobacter pylori）是胃炎、消化性溃疡疾病的病原体，并且是胃癌发展的危险因素。H.幽门螺杆菌感染在非洲是常见的，因为据报道尼日利亚高达85%的人口和南非65%的人口携带H。幽门。H.幽门螺杆菌的培养是非常挑剔的，并且这种病原体的诊断和治疗通常是困难的，特别是在非洲国家。我们刚刚在尼日利亚完成了一项流行病学研究，pylori毒力因子与H.幽门感染尼日利亚H.幽门螺杆菌菌株几乎一致地产生已知的主要毒力因子，例如功能性cag-T4 SS和s1 m1 vacA基因，然而，由这些菌株诱导的病理相对温和。此外，甲硝唑（99.1%）、阿莫西林（33.3%）和克拉霉素（14.4%）的中间体的抗生素耐药水平极高，但四环素的耐药水平令人惊讶地低（4.5%）。在这个新项目中，我们计划将我们的研究从尼日利亚扩展到南非，以获得关于非洲抗生素耐药性水平和菌株致病性的更全面的观点。南非是更古老的H. pylori菌株（例如hpAfrica 2），由于完全不存在cag-T4 SS，因此被认为致病性较低，我们希望将其与我们的尼日利亚hpAfrica 1分离株进行比较。有趣的是，我们的初步数据表明，除了23 S rRNA基因中已知的点突变外，还必须存在新的机制来提供H. pylori，将被研究。此外，除了确定南非菌株的毒力潜力外，我们还想研究非洲H. pylori菌株使用我们完善的蒙古沙鼠动物模型。通过交换已知的主要遗传决定因子（cagA基因、dupA基因座等），在致病性相当强的欧洲菌株B8和低致病性的尼日利亚和南非菌株之间，我们试图确定负责H.幽门螺杆菌致病我们的建议整合了来自尼日利亚、南非和德国的科学家，建立了一个德非网络，包括一个密集的博士教育项目。来自两个非洲国家的学生。我们的项目将使来自非洲的年轻科学家有机会了解欧洲的科学管理方式，从而为他们回国后提供更好的职业前景。

The Gram-negative bacterial pathogen Helicobacter pylori is the causative agent of gastritis, peptic ulcer disease and represents a risk factor for the development of gastric cancers. H. pylori infections are frequent in Africa, since up to 85% of the population of Nigeria and 65% in South Africa have been reported to carry H. pylori. H. pylori is fastidious to cultivate and diagnosis and treatment of this pathogen is often difficult, especially in African countries. We just finished an epidemiological study in Nigeria to correlate the expression of H. pylori virulence factors with gastroduodenal disease outcome induced by the H. pylori infection. Nigerian H. pylori strains nearly uniformly produce the known major virulence factors, e.g. a functional cag-T4SS and a s1m1 vacA gene, however, the pathology induced by these strains is relatively mild. Furthermore, antibiotic resistance levels were extremely high for metronidazole (99.1%), intermediate for amoxicillin (33.3%) and clarithromycin (14.4%), but surprisingly low for tetracycline (4.5%). In this novel project we plan to extend our studies from Nigeria to South Africa, to get a more global view about African antibiotic resistance levels and strain pathogenicity. South Africa is the origin of more ancient H. pylori strains (e.g. hpAfrica2) which are considered as less pathogenic due to a completely absent cag-T4SS, which we would like to compare to our Nigerian hpAfrica1 isolates. Interestingly, our preliminary data indicate that besides the known point mutations in 23S rRNA genes (a) novel mechanism(s) must exist(s) providing clarithromycin resistance in H. pylori, which will be studied. Furthermore, besides determining the virulence potential of South African strains we would like to study the basis for the mild pathology of African H. pylori strains using our well-established animal model of the Mongolian gerbils. By exchange of major known genetic determinants (cagA gene, dupA locus, etc.) between the rather pathogenic European strain B8 and low-pathogenic Nigerian and South African strains we try to identify genetic determinants responsible for the H. pylori-induced pathogenesis. Our proposal integrates scientists from both Nigeria, South Africa and Germany, establishing a German-African network, including an intense education program for Ph.D. students from both African countries. Our project will give young scientists from Africa a chance to learn how science is managed in Europe and therefore result in a better career perspective for them when going back to their own countries.