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

• Applicant: Professor Dr. Rainer Haas
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2015 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 271598711

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.

• DFG Programme: Research Grants
• International Connection: Nigeria, South Africa
• Co-Investigators: Friederike Aicher; Dr. Ute Breithaupt; Dr. Alexander Crispin; Dr. Olufunmilayo A. Lesi; Eva Löll; Privatdozentin Dr. Susanna Müller; Professor Dennis A. Ndububa; Dr. Charles A. Onyekwere; Professor Jesse A. Otegbayo; Dr. Sylvester Wokediuko
• International Co-Applicants: Professorin Dr. Anna M. Clarke, Ph.D. (†); Stella Smith, Ph.D.