Role of HK2 in the Enzootic Cycle of Borrelia burgdorferi

Frontiers in Medicine

article

Qiang Liu¹  Haijun Xu³  Yan Zhang¹  Jing Yang¹  Jimei Du¹  Yan Zhou¹  X. Frank Yang²  Yongliang Lou¹ 

[1] Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University;Department of Microbiology and Immunology, Indiana University School of Medicine, United States;State Key Laboratory of Rice Biology and Ministry of Agriculture Key Laboratory of Agricultural Entomology, Institute of Insect Sciences, Zhejiang University;Optometry and Eye Hospital and School of Ophthalmology, School of Biomedical Engineering, Wenzhou Medical University

关键词: lyme disease;    Borrelia (Borreliella) burgdorferi;    two-component system (TCS);    Rrp2-HK2;    OspC;   

DOI  :  10.3389/fmed.2020.573648

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

The two-component response regulator Rrp2 is a key activator controlling the production of numerous virulence factors of Borrelia burgdorferi , the Lyme disease pathogen. Previously it was shown that the cognate histidine kinase HK2 is not required for Rrp2 activation in vitro , nor for mammalian infection upon needle inoculation, raising the question whether HK2 has any role in the enzootic cycle of B. burgdorferi . In this study, we demonstrated that HK2 is not required for spirochetal survival in the tick vector. When fed on naive mice, the hk2 mutant had reduced infectivity through the route of tick bite, suggesting that the spirochetes lacking HK2 had a disadvantage in the enzootic cycle. Furthermore, overexpression of hk2 reduced the level of Rrp2 phosphorylation, suggesting that HK2 can function as a phosphatase to dephosphorylate Rrp2. Strains overexpressing hk2 impaired the expression of RpoN regulon whose activation is dependent on Rrp2 phosphorylation and activation, and had reduced infectivity in mice. Taken together, these results demonstrate that although HK2 does not play an essential role in Rrp2 activation, it is important for the optimal fitness of B. burgdorferi in the enzootic cycle.

【 授权许可】

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