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

分析淋病奈瑟菌和杜克雷嗜血杆菌的宿主受体结合特性

• 批准号: 405571442
• 负责人: Professor Dr. Christof Robert Hauck
• 金额: --
• 依托单位: Lehrstuhl Zellbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/405571442?language=en
• 关键词: Profiling; host; receptor; binding; properties

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.

淋病是全球最常见的性传播疾病（STD）之一。致病细菌淋病奈瑟氏菌正在迅速获得抗生素耐药性基因，而不可治疗的淋病的发生使WHO震惊。相比之下，嗜血杆菌的感染仅限于发展中国家，在这种国家中，该性病病原体导致了一种被忽视的热带疾病。致病性奈瑟氏菌和嗜血杆菌物种都在宿主的人类CECAMS上吸收了相同的受体。这种相互作用促进了粘膜的定殖。尽管CEACAM结合是感染起始的关键决定因素，但对于在淋病猪笼草和Ducreyi的非洲分离株中，CeacaM结合蛋白的患病率和特异性尚无。有趣的是，CEACAM蛋白的序列变体发生在非洲人群中，但是如果这些多态性改变了此类感染的易感性或疾病严重程度，则完全不镇定。因此，来自德国和南部非洲的3组采用互补的研究方法进行了合作研究这些普遍存在的人群，以及忽视了性病发病率的人群中的细菌病原体。我们的最终目标是开放新的翻译途径，以防止或治疗这些性病感染。作为直接目标，我们建议研究德班（南非）和马普托（Mozambique）城市社区中循环的淋球菌菌株的毒力因子 - 宿主结合谱，并将分离菌株的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H. ducreyi的原代分离株的宿主受体结合特性，并专注于H. ducreyi OMP P1蛋白，因为H. h. th. phenzae的同源物是CEACAM结合因子。为了补充以毒力为导向的，基于蛋白质的研究方面，我们将破译代表南非和莫桑比克循环的主要克隆谱系的淋球菌菌株的基因组。因此，我们将建立一个共同的基因组学平台来对淋球菌基因组进行序列，注释和比较。结合蛋白质生化和分析能力在合作伙伴实验室中建立的这些方法将成为表达和测试候选疫苗的基础，并在南部非洲的背景下评估其转化潜力。