Characterization of the Highly Regulated Antigen BBA05 in the Enzootic Cycle of
            <i>Borrelia burgdorferi</i>

Xu, Haijun; He, Ming; Pang, Xiujuan; Xu, Zao C.; Piesman, Joseph; Yang, Xiaofeng

doi:10.1128/iai.01008-09

Cited by 17 publications

(11 citation statements)

References 72 publications

(102 reference statements)

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“…BBA03 was chosen as the most likely candidate for this phenotype because of previous studies indicating that expression of this gene is upregulated during the tick blood meal (8,23) and because inactivation of other genes in this region did not have a negative impact on the spirochete's ability to successfully complete the infectious cycle (4,35,36,54,55). Our current findings indicate that BBA03 is a surface-exposed outer membrane lipoprotein that is upregulated during the tick blood meal.…”

Section: Discussionmentioning

confidence: 86%

Competitive Advantage of Borrelia burgdorferi with Outer Surface Protein BBA03 during Tick-Mediated Infection of the Mammalian Host

et al. 2012

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Linear plasmid lp54 is one of the most highly conserved and differentially expressed elements of the segmented genome of the Lyme disease spirochete Borrelia burgdorferi. We previously reported that deletion of a 4.1-kb region of lp54 (bba01 to bba07 [bba01-bba07]) led to a slight attenuation of tick-transmitted infection in mice following challenge with a large number of infected ticks. In the current study, we reduced the number of ticks in the challenge to more closely mimic the natural dose and found a profound defect in tick-transmitted infection of the bba01-bba07 mutant relative to wild-type B. burgdorferi. We next focused on deletion of bba03 as the most likely cause of this mutant phenotype, as previous studies have shown that expression of bba03 is increased by culture conditions that simulate tick feeding. Consistent with this hypothesis, we demonstrated increased expression of bba03 by spirochetes in fed relative to unfed ticks. We also observed that a bba03 deletion mutant, although fully competent by itself, did not efficiently infect mice when transmitted by ticks that were simultaneously coinfected with wild-type B. burgdorferi. These results suggest that BBA03 provides a competitive advantage to spirochetes carrying this protein during tick transmission to a mammalian host in the natural infectious cycle.T he genome of Borrelia burgdorferi, the causative agent of Lyme disease, consists of a linear chromosome and numerous linear and circular plasmids (9,15). Several of these extrachromosomal plasmids have been shown to carry genes that are critical for B. burgdorferi viability during the infectious cycle, as it must adapt to two very different environments, i.e., the Ixodes tick vector and a mammalian host (18,25,38,39,57). One of the most highly conserved plasmids, which also has one of the largest proportions of differentially regulated genes in the B. burgdorferi genome, is the linear plasmid lp54 (7,10,21,30,32,39,40,44,51,52,56). Although several genes on lp54 have been identified as contributing to (5,14,41,48) or essential for (3,39,58) spirochete fitness in vivo, the majority of the proteins encoded on this plasmid are of unknown function and lack homologs in other organisms (9,15). We previously used the Cre-lox system to delete the genes encompassing a 4.1-kb region of lp54, from bba01 to bba07 (bba01-bba07 region) (A3⌬A1-7 mutant) (4). In addition to a delay in colony formation and distinct colony morphology, a slight defect was observed in the ability of the A3⌬A1-7 mutant to establish mammalian infection by tick bite in a challenge with 20 infected nymphs per mouse. In this study, to create a more biologically relevant model, we reduced the tick challenge to 3 ticks per mouse and found that the A3⌬A1-7 mutant was significantly attenuated in the ability to infect mice by tick bite in this challenge, whereas wild-type (WT) B. burgdorferi could routinely establish mammalian infection at a dose as low as 1 tick per mouse.Since all attempts to complement the full A3⌬A1-7 mutant were unsuc...

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Section: Discussionmentioning

confidence: 86%

Competitive Advantage of Borrelia burgdorferi with Outer Surface Protein BBA03 during Tick-Mediated Infection of the Mammalian Host

et al. 2012

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“…Recent research investigating borrelia-vector interactions have focused on inactivation of global regulators, individual genes, and replicons to advance our understanding of B. burgdorferi tick colonization and persistence and vector transmission mechanisms (1,4,7,18,(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54). The loss of BBA66 activity did not completely abolish the ability of B. burgdorferi to invade the host by tick bite (at least when more than 4 ticks/mouse fed to repletion), but mouse infectivity was significantly impaired.…”

Section: Discussionmentioning

confidence: 99%

Borrelia burgdorferi bba66 Gene Inactivation Results in Attenuated Mouse Infection by Tick Transmission

et al. 2013

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bThe impact of the Borrelia burgdorferi surface-localized immunogenic lipoprotein BBA66 on vector and host infection was evaluated by inactivating the encoding gene, bba66, and characterizing the mutant phenotype throughout the natural mouse-tickmouse cycle. The BBA66-deficient mutant isolate, Bb ⌬A66 , remained infectious in mice by needle inoculation of cultured organisms, but differences in spirochete burden and pathology in the tibiotarsal joint were observed relative to the parental wild-type (WT) strain. Ixodes scapularis larvae successfully acquired Bb ⌬A66 following feeding on infected mice, and the organisms persisted in these ticks through the molt to nymphs. A series of tick transmission experiments (n ‫؍‬ 7) demonstrated that the ability of Bb ⌬A66 -infected nymphs to infect laboratory mice was significantly impaired compared to that of mice fed upon by WT-infected ticks. trans-complementation of Bb ⌬A66 with an intact copy of bba66 restored the WT infectious phenotype in mice via tick transmission. These results suggest a role for BBA66 in facilitating B. burgdorferi dissemination and transmission from the tick vector to the mammalian host as part of the disease process for Lyme borreliosis.

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“…Chemical determinants in the bloodmeal and changes in physical environmental conditions signal B. burgdorferi to differentially express genes encoding products presumably required for this dissemination. Several borrelial genes have been shown to be expressed within feeding ticks (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18), but specific gene products and mechanisms that facilitate B. burgdorferi migration from the tick to the host are unknown.…”

mentioning

confidence: 99%

The bba64 gene of Borrelia burgdorferi , the Lyme disease agent, is critical for mammalian infection via tick bite transmission

Gilmore

Howison²,

Dietrich³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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The spirochetal agent of Lyme disease, Borrelia burgdorferi , is transmitted by bites of Ixodes ticks to mammalian reservoir hosts and humans. The mechanism(s) by which the organism is trafficked from vector to host is poorly understood. In this study, we demonstrate that a B. burgdorferi mutant strain deficient in the synthesis of the bba64 gene product was incapable of infecting mice via tick bite even though the mutant was ( i ) infectious in mice when introduced by needle inoculation, ( ii ) acquired by larval ticks feeding on infected mice, and ( iii ) able to persist through tick molting stages. This finding of a B. burgdorferi gene required for pathogen transfer and/or survival from the tick to the susceptible host represents an important breakthrough toward understanding transmission mechanisms involved for the Lyme disease agent.

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Characterization of the Highly Regulated Antigen BBA05 in the Enzootic Cycle of Borrelia burgdorferi

Cited by 17 publications

References 72 publications

Competitive Advantage of Borrelia burgdorferi with Outer Surface Protein BBA03 during Tick-Mediated Infection of the Mammalian Host

Competitive Advantage of Borrelia burgdorferi with Outer Surface Protein BBA03 during Tick-Mediated Infection of the Mammalian Host

Borrelia burgdorferi bba66 Gene Inactivation Results in Attenuated Mouse Infection by Tick Transmission

The bba64 gene of Borrelia burgdorferi , the Lyme disease agent, is critical for mammalian infection via tick bite transmission

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