YebC regulates variable surface antigen VlsE expression and is required for host immune evasion in Borrelia burgdorferi.

Borrelia burgdorferi, the Lyme disease pathogen causes persistent infection by evading the host immune response. Differential expression of the surface-exposed lipoprotein VlsE that undergoes antigenic variation is a key immune evasion strategy employed by B. burgdorferi. Most studies focused on the...

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Autores principales:	Yan Zhang, Tong Chen, Sajith Raghunandanan, Xuwu Xiang, Jing Yang, Qiang Liu, Diane G Edmondson, Steven J Norris, X Frank Yang, Yongliang Lou
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2020
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7b59ca5223f54931bcc9e9c515f40271
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spelling	oai:doaj.org-article:7b59ca5223f54931bcc9e9c515f402712021-12-02T19:59:38ZYebC regulates variable surface antigen VlsE expression and is required for host immune evasion in Borrelia burgdorferi.1553-73661553-737410.1371/journal.ppat.1008953https://doaj.org/article/7b59ca5223f54931bcc9e9c515f402712020-10-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1008953https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Borrelia burgdorferi, the Lyme disease pathogen causes persistent infection by evading the host immune response. Differential expression of the surface-exposed lipoprotein VlsE that undergoes antigenic variation is a key immune evasion strategy employed by B. burgdorferi. Most studies focused on the mechanism of VlsE antigen variation, but little is known about VlsE regulation and factor(s) that regulates differential vlsE expression. In this study, we investigated BB0025, a putative YebC family transcriptional regulator (and hence designated BB0025 as YebC of B. burgdorferi herein). We constructed yebC mutant and complemented strain in an infectious strain of B. burgdorferi. The yebC mutant could infect immunocompromised SCID mice but not immunocompetent mice, suggesting that YebC plays an important role in evading host adaptive immunity. RNA-seq analyses identified vlsE as one of the genes whose expression was most affected by YebC. Quantitative RT-PCR and Western blot analyses confirmed that vlsE expression was dependent on YebC. In vitro, YebC and VlsE were co-regulated in response to growth temperature. In mice, both yebC and vlsE were inversely expressed with ospC in response to the host adaptive immune response. Furthermore, EMSA proved that YebC directly binds to the vlsE promoter, suggesting a direct transcriptional control. These data demonstrate that YebC is a new regulator that modulates expression of vlsE and other genes important for spirochetal infection and immune evasion in the mammalian host.Yan ZhangTong ChenSajith RaghunandananXuwu XiangJing YangQiang LiuDiane G EdmondsonSteven J NorrisX Frank YangYongliang LouPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 16, Iss 10, p e1008953 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Yan Zhang Tong Chen Sajith Raghunandanan Xuwu Xiang Jing Yang Qiang Liu Diane G Edmondson Steven J Norris X Frank Yang Yongliang Lou YebC regulates variable surface antigen VlsE expression and is required for host immune evasion in Borrelia burgdorferi.
description	Borrelia burgdorferi, the Lyme disease pathogen causes persistent infection by evading the host immune response. Differential expression of the surface-exposed lipoprotein VlsE that undergoes antigenic variation is a key immune evasion strategy employed by B. burgdorferi. Most studies focused on the mechanism of VlsE antigen variation, but little is known about VlsE regulation and factor(s) that regulates differential vlsE expression. In this study, we investigated BB0025, a putative YebC family transcriptional regulator (and hence designated BB0025 as YebC of B. burgdorferi herein). We constructed yebC mutant and complemented strain in an infectious strain of B. burgdorferi. The yebC mutant could infect immunocompromised SCID mice but not immunocompetent mice, suggesting that YebC plays an important role in evading host adaptive immunity. RNA-seq analyses identified vlsE as one of the genes whose expression was most affected by YebC. Quantitative RT-PCR and Western blot analyses confirmed that vlsE expression was dependent on YebC. In vitro, YebC and VlsE were co-regulated in response to growth temperature. In mice, both yebC and vlsE were inversely expressed with ospC in response to the host adaptive immune response. Furthermore, EMSA proved that YebC directly binds to the vlsE promoter, suggesting a direct transcriptional control. These data demonstrate that YebC is a new regulator that modulates expression of vlsE and other genes important for spirochetal infection and immune evasion in the mammalian host.
format	article
author	Yan Zhang Tong Chen Sajith Raghunandanan Xuwu Xiang Jing Yang Qiang Liu Diane G Edmondson Steven J Norris X Frank Yang Yongliang Lou
author_facet	Yan Zhang Tong Chen Sajith Raghunandanan Xuwu Xiang Jing Yang Qiang Liu Diane G Edmondson Steven J Norris X Frank Yang Yongliang Lou
author_sort	Yan Zhang
title	YebC regulates variable surface antigen VlsE expression and is required for host immune evasion in Borrelia burgdorferi.
title_short	YebC regulates variable surface antigen VlsE expression and is required for host immune evasion in Borrelia burgdorferi.
title_full	YebC regulates variable surface antigen VlsE expression and is required for host immune evasion in Borrelia burgdorferi.
title_fullStr	YebC regulates variable surface antigen VlsE expression and is required for host immune evasion in Borrelia burgdorferi.
title_full_unstemmed	YebC regulates variable surface antigen VlsE expression and is required for host immune evasion in Borrelia burgdorferi.
title_sort	yebc regulates variable surface antigen vlse expression and is required for host immune evasion in borrelia burgdorferi.
publisher	Public Library of Science (PLoS)
publishDate	2020
url	https://doaj.org/article/7b59ca5223f54931bcc9e9c515f40271
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YebC regulates variable surface antigen VlsE expression and is required for host immune evasion in Borrelia burgdorferi.

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