BBA52 Facilitates<i>Borrelia burgdorferi</i>Transmission from Feeding Ticks to Murine Hosts

Kumar, Manish; Yang, Xiuli; Coleman, Adam S.; Pal, Utpal

doi:10.1086/651172

Cited by 49 publications

(88 citation statements)

References 50 publications

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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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Section: Discussionmentioning

confidence: 99%

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

et al. 2013

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“…RNA samples for quantitative reverse transcription-PCR (qRT-PCR) analysis were prepared as previously described (25,57,66). Briefly, total RNAs from mouse tissues and ticks were isolated using TRIzol reagent (Invitrogen, Carlsbad, CA), and contaminating genomic DNA was removed using Turbo DNase (Ambion, Austin, TX).…”

Section: Methodsmentioning

confidence: 99%

Borrelia burgdorferi Needs Chemotaxis To Establish Infection in Mammals and To Accomplish Its Enzootic Cycle

et al. 2012

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ABSTRACTBorrelia burgdorferi, the causative agent of Lyme disease, can be recovered from different organs of infected animals and patients, indicating that the spirochete is very invasive. Motility and chemotaxis contribute to the invasiveness ofB. burgdorferiand play important roles in the process of the disease. Recent reports have shown that motility is required for establishing infection in mammals. However, the role of chemotaxis in virulence remains elusive. Our previous studies showed thatcheA2, a gene encoding a histidine kinase, is essential for the chemotaxis ofB. burgdorferi. In this report, thecheA2gene was inactivated in a low-passage-number virulent strain ofB. burgdorferi. In vitroanalyses (microscopic observations, computer-based bacterial tracking analysis, swarm plate assays, and capillary tube assays) showed that thecheA2mutant failed to reverse and constantly ran in one direction; the mutant was nonchemotactic to attractants. Mouse needle infection studies showed that thecheA2mutant failed to infect either immunocompetent or immunodeficient mice and was quickly eliminated from the initial inoculation sites. Tick-mouse infection studies revealed that although the mutant was able to survive in ticks, it failed to establish a new infection in mice via tick bites. The altered phenotypes were completely restored when the mutant was complemented. Collectively, these data demonstrate thatB. burgdorferineeds chemotaxis to establish mammalian infection and to accomplish its natural enzootic cycle.

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“…Four-to sixweek-old female C3H/HeN mice were purchased from the National Institutes of Health. The ticks used in the present study were reared in the laboratory as described elsewhere (29). All animal experiments were performed in accordance with the guidelines of the Institutional Biosafety Committee and the Institutional Animal Care and Use Committee.…”

Section: Methodsmentioning

confidence: 99%

A Surface Enolase Participates in Borrelia burgdorferi-Plasminogen Interaction and Contributes to Pathogen Survival within Feeding Ticks

et al. 2012

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Borrelia burgdorferi, a tick-borne bacterial pathogen, causes a disseminated infection involving multiple organs known as Lyme disease. Surface proteins can directly participate in microbial virulence by facilitating pathogen dissemination via interaction with host factors. We show here that a fraction of the B. burgdorferi chromosomal gene product BB0337, annotated as enolase or phosphopyruvate dehydratase, is associated with spirochete outer membrane and is surface exposed. B. burgdorferi enolase, either in a recombinant form or as a membrane-bound native antigen, displays enzymatic activities intrinsic to the glycolytic pathway. However, the protein also interacts with host plasminogen, potentially leading to its activation and resulting in B. burgdorferi-induced fibrinolysis. As expected, enolase displayed consistent expression in vivo, however, with a variable temporal and spatial expression during spirochete infection in mice and ticks. Despite an extracellular exposure of the antigen and a potential role in host-pathogen interaction, active immunization of mice with recombinant enolase failed to evoke protective immunity against subsequent B. burgdorferi infection. In contrast, enolase immunization of murine hosts significantly reduced the acquisition of spirochetes by feeding ticks, suggesting that the protein could have a stage-specific role in B. burgdorferi survival in the feeding vector. Strategies to interfere with the function of surface enolase could contribute to the development of novel preventive measures to interrupt the spirochete infection cycle and reduce the incidences of Lyme disease.

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BBA52 FacilitatesBorrelia burgdorferiTransmission from Feeding Ticks to Murine Hosts

Cited by 49 publications

References 50 publications

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

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

Borrelia burgdorferi Needs Chemotaxis To Establish Infection in Mammals and To Accomplish Its Enzootic Cycle

A Surface Enolase Participates in Borrelia burgdorferi-Plasminogen Interaction and Contributes to Pathogen Survival within Feeding Ticks

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