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Role of HK2 in the Enzootic Cycle of Borrelia burgdorferi
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 infe...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649798/ https://www.ncbi.nlm.nih.gov/pubmed/33195322 http://dx.doi.org/10.3389/fmed.2020.573648 |
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author | Liu, Qiang Xu, Haijun Zhang, Yan Yang, Jing Du, Jimei Zhou, Yan Yang, X. Frank Lou, Yongliang |
author_facet | Liu, Qiang Xu, Haijun Zhang, Yan Yang, Jing Du, Jimei Zhou, Yan Yang, X. Frank Lou, Yongliang |
author_sort | Liu, Qiang |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7649798 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-76497982020-11-13 Role of HK2 in the Enzootic Cycle of Borrelia burgdorferi Liu, Qiang Xu, Haijun Zhang, Yan Yang, Jing Du, Jimei Zhou, Yan Yang, X. Frank Lou, Yongliang Front Med (Lausanne) Medicine 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. Frontiers Media S.A. 2020-10-26 /pmc/articles/PMC7649798/ /pubmed/33195322 http://dx.doi.org/10.3389/fmed.2020.573648 Text en Copyright © 2020 Liu, Xu, Zhang, Yang, Du, Zhou, Yang and Lou. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Medicine Liu, Qiang Xu, Haijun Zhang, Yan Yang, Jing Du, Jimei Zhou, Yan Yang, X. Frank Lou, Yongliang Role of HK2 in the Enzootic Cycle of Borrelia burgdorferi |
title | Role of HK2 in the Enzootic Cycle of Borrelia burgdorferi |
title_full | Role of HK2 in the Enzootic Cycle of Borrelia burgdorferi |
title_fullStr | Role of HK2 in the Enzootic Cycle of Borrelia burgdorferi |
title_full_unstemmed | Role of HK2 in the Enzootic Cycle of Borrelia burgdorferi |
title_short | Role of HK2 in the Enzootic Cycle of Borrelia burgdorferi |
title_sort | role of hk2 in the enzootic cycle of borrelia burgdorferi |
topic | Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649798/ https://www.ncbi.nlm.nih.gov/pubmed/33195322 http://dx.doi.org/10.3389/fmed.2020.573648 |
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