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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: Zhang, Yan, Chen, Tong, Raghunandanan, Sajith, Xiang, Xuwu, Yang, Jing, Liu, Qiang, Edmondson, Diane G., Norris, Steven J., Yang, X. Frank, Lou, Yongliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584230/
https://www.ncbi.nlm.nih.gov/pubmed/33048986
http://dx.doi.org/10.1371/journal.ppat.1008953
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author Zhang, Yan
Chen, Tong
Raghunandanan, Sajith
Xiang, Xuwu
Yang, Jing
Liu, Qiang
Edmondson, Diane G.
Norris, Steven J.
Yang, X. Frank
Lou, Yongliang
author_facet Zhang, Yan
Chen, Tong
Raghunandanan, Sajith
Xiang, Xuwu
Yang, Jing
Liu, Qiang
Edmondson, Diane G.
Norris, Steven J.
Yang, X. Frank
Lou, Yongliang
author_sort Zhang, Yan
collection PubMed
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.
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spelling pubmed-75842302020-10-28 YebC regulates variable surface antigen VlsE expression and is required for host immune evasion in Borrelia burgdorferi Zhang, Yan Chen, Tong Raghunandanan, Sajith Xiang, Xuwu Yang, Jing Liu, Qiang Edmondson, Diane G. Norris, Steven J. Yang, X. Frank Lou, Yongliang PLoS Pathog Research Article 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. Public Library of Science 2020-10-13 /pmc/articles/PMC7584230/ /pubmed/33048986 http://dx.doi.org/10.1371/journal.ppat.1008953 Text en © 2020 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Zhang, Yan
Chen, Tong
Raghunandanan, Sajith
Xiang, Xuwu
Yang, Jing
Liu, Qiang
Edmondson, Diane G.
Norris, Steven J.
Yang, X. Frank
Lou, Yongliang
YebC regulates variable surface antigen VlsE expression and is required for host immune evasion in Borrelia burgdorferi
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584230/
https://www.ncbi.nlm.nih.gov/pubmed/33048986
http://dx.doi.org/10.1371/journal.ppat.1008953
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