Profiling the host receptor binding properties of Neisseria gonorrhoeae and Haemophilus ducreyi

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Gonorrhoea is one of the most common sexually transmitted diseases (STD) worldwide. The causative bacterium, Neisseria gonorrhoeae, is rapidly acquiring antibiotic resistance genes and the occurance of untreatable gonorrhoea has alarmed the WHO. In contrast, Haemophilus ducreyi infections are restricted to developing countries, where this STD pathogen is responsible for chancroid, a neglected tropical disease. Both pathogenic Neisseria and Haemophilus species engage the same group of receptors on the host side, human CEACAMs. This interaction facilitates the colonization of the mucosa. Though CEACAM binding is a critical determinant of infection initiation, nothing is known about the prevalence and specificity of CEACAM-binding adhesins in african isolates of N. gonorrhoeae and H. ducreyi. Interestingly, sequence variants of CEACAM proteins occur in african populations, but if these polymorphisms alter the susceptibility or disease severity of such infections is completely unkown. Therefore, 3 groups from Germany and southern Africa with complementary research approaches have teamed up to study these prevalent as well as neglected bacterial pathogens in a population with a high incidence of STDs. Our ultimate goal is to open new translational avenues to prevent or treat these venereal infections. As immediate goals, we propose to study the virulence factor-host binding profile of gonococcal strains circulating in the urban communities of Durban (South Africa) and Maputo (Mozambique) and to link the CEACAM binding patterns of isolated strains with the CEACAM allele composition of the corresponding infected person. In parallel, we will investigate the host receptor binding properties of primary isolates of H. ducreyi and focus on the H. ducreyi OMP P1 protein, as the homologue from H. influenzae is the CEACAM-binding factor. To complement the virulence-factor oriented, protein-based research aspect of this collaboration we will decipher the genomes of gonococcal strains representing major clonal lineages circulating in South Africa and Mozambique. Thereby, we will establish a common genomics platform to sequence, annotate, and compare gonococcal genomes. Combined with the protein biochemical and analytical capabilities build up in the partner labs these approaches will serve as a basis for expressing and testing vaccine candidates and evaluating their translational potential in the context of southern Africa.