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

淋病是全世界最常见的性传播疾病之一。引起淋病的细菌奈瑟氏菌正在迅速获得抗药性基因，无法治愈的淋病的发生已经向世卫组织发出了警告。相比之下，杜雷伊嗜血杆菌的感染仅限于发展中国家，在这些国家，这种STD病原体是一种被忽视的热带疾病--下巴的罪魁祸首。致病奈瑟氏菌和嗜血杆菌都与宿主一侧的同一组受体--人CEACAM结合。这种相互作用促进了粘膜的定植。虽然CEACAM结合是感染启动的一个关键决定因素，但关于CEACAM结合粘附素在非洲淋球菌和杜氏杆菌分离株中的流行率和特异性尚不清楚。有趣的是，CEACAM蛋白的序列变异存在于非洲人群中，但如果这些多态改变了此类感染的易感性或疾病严重性，则完全未知。因此，来自德国和南部非洲的3个研究小组以互补的研究方法联合起来，在性传播疾病高发人群中研究这些流行的和被忽视的细菌病原体。我们的最终目标是开辟新的翻译途径来预防或治疗这些性病感染。作为近期目标，我们建议研究在南非德班和莫桑比克马普托城市社区流行的淋球菌毒力因子-宿主结合谱，并将分离株的CEACAM结合模式与相应感染者的CEACAM等位基因组成联系起来。同时，我们将研究杜氏嗜血杆菌初级分离株的宿主受体结合特性，并重点研究杜氏嗜血杆菌OMP P1蛋白，因为流感嗜血杆菌的同源物是CEACAM结合因子。为了补充这一合作中以毒力因子为导向、基于蛋白质的研究方面，我们将破译代表在南非和莫桑比克流行的主要克隆谱系的淋球菌菌株的基因组。因此，我们将建立一个通用的基因组学平台来对淋球菌基因组进行测序、注释和比较。结合伙伴实验室建立的蛋白质、生化和分析能力，这些方法将作为表达和测试候选疫苗并评估其在南部非洲的翻译潜力的基础。

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.