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

革兰氏阴性细菌幽门螺杆菌是胃炎、消化性溃疡疾病的病原体，也是胃癌发展的危险因素。幽门螺杆菌感染在非洲很常见，因为据报道，尼日利亚高达85%的人口和南非65%的人口携带幽门螺杆菌。幽门螺旋杆菌很难培养，这种病原体的诊断和治疗往往很困难，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，目的是研究幽门螺杆菌毒力因子的表达与幽门螺杆菌感染引起的胃十二指肠疾病的预后之间的关系。尼日利亚幽门螺杆菌菌株几乎一致产生已知的主要毒力因子，如功能性的cag-T4SS和s1m1 vacA基因，但这些菌株引起的病理相对较轻。此外，甲硝唑（99.1%）、阿莫西林（33.3%）和克拉霉素（14.4%）的耐药水平极高，但四环素的耐药水平却低得惊人（4.5%）。在这个新颖的项目中，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。南非是更古老的幽门螺杆菌菌株（例如hpAfrica2）的起源，由于完全没有cag-T4SS，因此被认为致病性较低，我们希望将其与尼日利亚的hpAfrica1分离株进行比较。有趣的是，我们的初步数据表明，除了已知的23S rRNA基因点突变外，幽门螺杆菌中一定存在提供克拉霉素耐药的新机制，我们将对此进行研究。此外，除了确定南非菌株的毒力潜力外，我们还希望利用我们建立的蒙古沙鼠动物模型研究非洲幽门螺杆菌菌株轻度病理学的基础。通过在致病性较强的欧洲菌株B8与致病性较低的尼日利亚和南非菌株之间交换已知的主要遗传决定因素（cagA基因、dupA基因座等），我们试图确定与幽门螺杆菌致病机制有关的遗传决定因素。我们的提议整合了尼日利亚、南非和德国的科学家，建立了一个德国-非洲网络，包括一个针对来自这两个非洲国家的博士生的强化教育项目。我们的项目将使来自非洲的年轻科学家有机会了解欧洲是如何管理科学的，从而为他们回到自己的国家后带来更好的职业前景。

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.