Changing of the guard: How the Lyme disease spirochete subverts the host immune response

Chaconas, George; Castellanos, Mildred; Verhey, Theodore B.

doi:10.1074/jbc.rev119.008583

Cited by 36 publications

(55 citation statements)

References 96 publications

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“…One of the unique features of B . burgdorferi infection is the ability of the spirochete to evade immune responses and maintain a persistent infection in the mammalian host [ 1 , 52 ]. Antigen variation and differential expression of VlsE plays a critical role in this process [ 46 , 50 – 52 ].…”

Section: Discussionmentioning

confidence: 99%

“…burgdorferi infection is the ability of the spirochete to evade immune responses and maintain a persistent infection in the mammalian host [ 1 , 52 ]. Antigen variation and differential expression of VlsE plays a critical role in this process [ 46 , 50 – 52 ]. Over the past two decades, while much information regarding Borrelia gene regulation has been revealed, limited is known about regulation of vlsE expression [ 2 , 6 , 49 , 51 , 65 – 67 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, more IR sequences are reported in other B . burgdorferi strains [ 52 ]. The Function of this IR in vlsE expression remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, another surface-exposed lipoprotein, VlsE, which is structurally similar to OspC but antigenically variable, is upregulated [ 47 , 49 , 50 ]. Antigen variation of VlsE is achieved via gene conversion that occurs between the expressing vlsE locus and the adjacent 15 silent cassettes, each of which contains six VlsE antigenic variable regions [ 50 – 52 ]. Spirochetes lacking vlsE are able to maintain persistent infection in immunocompromised mice, but are unable to sustain infection in immunocompetent mice [ 53 – 57 ].…”

Section: Introductionmentioning

confidence: 99%

“…Spirochetes lacking vlsE are able to maintain persistent infection in immunocompromised mice, but are unable to sustain infection in immunocompetent mice [ 53 – 57 ]. Despite the importance of VlsE in immune evasion, very little is known about the mechanism of differential expression of vlsE [ 51 , 52 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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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