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

Authors :
Yan Zhang
Tong Chen
Sajith Raghunandanan
Xuwu Xiang
Jing Yang
Qiang Liu
Diane G Edmondson
Steven J Norris
X Frank Yang
Yongliang Lou
Source :
PLoS Pathogens, Vol 16, Iss 10, p e1008953 (2020)
Publication Year :
2020
Publisher :
Public Library of Science (PLoS), 2020.

Abstract

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.

Details

Language :
English
ISSN :
15537366 and 15537374
Volume :
16
Issue :
10
Database :
Directory of Open Access Journals
Journal :
PLoS Pathogens
Publication Type :
Academic Journal
Accession number :
edsdoj.7b59ca5223f54931bcc9e9c515f40271
Document Type :
article
Full Text :
https://doi.org/10.1371/journal.ppat.1008953