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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...

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Autores principales: Liu, Qiang, Xu, Haijun, Zhang, Yan, Yang, Jing, Du, Jimei, Zhou, Yan, Yang, X. Frank, Lou, Yongliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
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.
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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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