Yadav Ravi, Noinaj Nicholas, Ostan Nicholas, Moraes Trevor, Stoudenmire Julie, Maurakis Stavros, Cornelissen Cynthia Nau
Markey Center for Structural Biology, Department of Biological Sciences, Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN, United States.
Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
Front Microbiol. 2020 Jan 10;10:2981. doi: 10.3389/fmicb.2019.02981. eCollection 2019.
The pathogenic species are human-adapted pathogens that cause quite distinct diseases. causes the common sexually transmitted infection gonorrhea, while causes a potentially lethal form of bacterial meningitis. During infection, both pathogens deploy a number of virulence factors in order to thrive in the host. The focus of this review is on the outer membrane transport systems that enable the to utilize host-specific nutrients, including metal-binding proteins such as transferrin and calprotectin. Because acquisition of these critical metals is essential for growth and survival, understanding the structures of receptor-ligand complexes may be an important step in developing preventative or therapeutic strategies focused on thwarting these pathogens. Much can also be learned by comparing structures with antigenic diversity among the transporter sequences, as conserved functional domains in these essential transporters could represent the pathogens' "Achilles heel." Toward this goal, we present known or modeled structures for the transport systems produced by the pathogenic species, overlapped with sequence diversity derived by comparing hundreds of neisserial protein sequences. Given the concerning increase in incidence and antibiotic resistance, these outer membrane transport systems appear to be excellent targets for new therapies and preventative vaccines.
致病菌种是适应人类的病原体，会引发截然不同的疾病。淋病奈瑟菌会导致常见的性传播感染淋病，而脑膜炎奈瑟菌会引发一种可能致命的细菌性脑膜炎。在感染过程中，这两种病原体都会部署多种毒力因子以便在宿主体内繁衍。本综述的重点是外膜转运系统，该系统使淋病奈瑟菌能够利用宿主特异性营养物质，包括金属结合蛋白，如转铁蛋白和钙卫蛋白。由于获取这些关键金属对于生长和存活至关重要，了解受体-配体复合物的结构可能是制定针对这些病原体的预防或治疗策略的重要一步。通过比较转运蛋白序列中的结构与抗原多样性也可以学到很多东西，因为这些必需转运蛋白中的保守功能域可能代表病原体的“阿喀琉斯之踵”。为了实现这一目标，我们展示了致病奈瑟菌种产生的转运系统的已知或模拟结构，并与通过比较数百个奈瑟菌蛋白质序列得出的序列多样性重叠。鉴于淋病发病率和抗生素耐药性令人担忧地增加，这些外膜转运系统似乎是新疗法和预防性疫苗的极佳靶点。
