Preferential Presence of Decorin-Binding Protein B (BBA25) and BBA50 Antibodies in Cerebrospinal Fluid of Patients with Neurologic Lyme Disease

Fikrig, Erol; Coyle, Patricia K.; Schutzer, Steven E.; Chen, Manchuan; Deng, Zhidian; Flavell, Richard A.

doi:10.1128/jcm.42.3.1243-1246.2004

Cited by 10 publications

(7 citation statements)

References 27 publications

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“…These enzymes linked by an activation cascade may lead to the focal and transient degradation of tight junction proteins that allows B. burgdorferi to invade the CNS, yet our preliminary experiments indicated that B. burgdorferi cells could bind via their tips prior to crossing the in vitro human BBB model (data not shown) and that they did so without evidence of breakdown of the BBB integrity based on endpoint Endohm TEER measurements. The TEER and permeability data are consistent with what has been observed in vivo; i.e., unlike what is seen in purulent bacterial meningitis, B. burgdorferi infection usually causes aseptic meningitis in which the permeability of the BBB is not substantially altered (18).…”

Section: Discussionsupporting

confidence: 76%

Borrelia burgdorferi, Host-Derived Proteases, and the Blood-Brain Barrier

Grab¹,

et al. 2005

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Neurological manifestations of Lyme disease in humans are attributed in part to penetration of the blood-brain barrier (BBB) and invasion of the central nervous system (CNS) by Borrelia burgdorferi. However, how the spirochetes cross the BBB remains an unresolved issue. We examined the traversal of B. burgdorferi across the human BBB and systemic endothelial cell barriers using in vitro model systems constructed of human brain microvascular endothelial cells (BMEC) and EA.hy 926, a human umbilical vein endothelial cell (HUVEC) line grown on Costar Transwell inserts. These studies showed that B. burgdorferi differentially crosses human BMEC and HUVEC and that the human BMEC form a barrier to traversal. During the transmigration by the spirochetes, it was found that the integrity of the endothelial cell monolayers was maintained, as assessed by transendothelial electrical resistance measurements at the end of the experimental period, and that B. burgdorferi appeared to bind human BMEC by their tips near or at cell borders, suggesting a paracellular route of transmigration. Importantly, traversal of B. burgdorferi across human BMEC induces the expression of plasminogen activators, plasminogen activator receptors, and matrix metalloproteinases. Thus, the fibrinolytic system linked by an activation cascade may lead to focal and transient degradation of tight junction proteins that allows B. burgdorferi to invade the CNS.

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Section: Discussionsupporting

confidence: 76%

Borrelia burgdorferi, Host-Derived Proteases, and the Blood-Brain Barrier

Grab¹,

et al. 2005

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“…This may be due to differences in technique or the arrayed stocks of these mutants may be contaminated with infectious mutants that masked the infectivity defect. Experimentally, antibodies recognizing BBA50 and BBA51 have been found in the cerebral spinal fluid and sera of patients with neurologic Lyme disease suggesting that they may be present on the bacterial surface at some point during vertebrate infection (Fikrig et al ., ). Together with bba48 , bba50 and bba51 may constitute an operon contributing to bacterial fitness during infection.…”

Section: Resultsmentioning

confidence: 97%

Global Tn‐seq analysis of carbohydrate utilization and vertebrate infectivity of Borrelia burgdorferi

Troy

Lin

Gao

et al. 2016

Molecular Microbiology

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SUMMARY Borrelia burgdorferi maintains a complex life cycle between tick and vertebrate hosts. Although some genes have been identified as contributing to bacterial adaptation in the different hosts, the list is incomplete. In this manuscript, we report the first use of transposon mutagenesis combined with high-throughput sequencing (Tn-seq) in B. burgdorferi. We utilize the technique to investigate mechanisms of carbohydrate utilization in B. burgdorferi and the role of carbohydrate metabolism during mouse infection. We performed genetic fitness analyses to identify genes encoding factors contributing to growth on glucose, maltose, mannose, trehalose, and N-acetyl-glucosamine. We obtained insight into the potential functions of proteins predicted to be involved in carbohydrate utilization and identified additional factors previously unrecognized as contributing to the metabolism of the tested carbohydrates. Strong phenotypes were observed for the putative carbohydrate phosphotransferase transporters BB0408 and BBB29 as well as the response regulator Rrp1. We further validated Tn-seq for use in mouse studies and were able to correctly identify known infectivity factors as well as additional transporters and genes on lp54 that may contribute to optimal mouse infection. As such, this study establishes Tn-seq as a powerful method for both in vitro and in vivo studies of B. burgdorferi.

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“…B. burgdorferi bacteria within the midguts of unfed ticks are relatively somnolent and probably do not divide for months on end, whereas tick feeding induces rapid borrelial growth and division times on the order of 1 to 2 h per cycle (12,22,67,68,69,87). It is probably not a coincidence that several genes associated with mammalian infection are both positively influenced by EbfC and upregulated during transmission (26,27,34,35,36,38,39,48,60,66,79,80). Conversely, the current studies found that EbfC repressed transcription of oms28/ORF BBA74, a gene that is expressed during tick colonization but not during vertebrate infection (64).…”

Section: Discussionmentioning

confidence: 99%

“…The positively affected dbpB gene encodes decorin-binding protein B, an outer surface protein involved with adherence to host tissues during mammalian infection (26,27,28,37,38,79,80). B. burgdorferi encodes two proteins that show similarity to the E. coli xylose-responsive regulatory protein, XylR-1 and XylR-2 (32).…”

Section: Ebfc Is a Nucleoid-associated Proteinmentioning

confidence: 99%

EbfC (YbaB) Is a New Type of Bacterial Nucleoid-Associated Protein and a Global Regulator of Gene Expression in the Lyme Disease Spirochete

et al. 2012

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Nearly every known species of Eubacteria encodes a homolog of the Borrelia burgdorferi EbfC DNA-binding protein. We now demonstrate that fluorescently tagged EbfC associates with B. burgdorferi nucleoids in vivo and that chromatin immunoprecipitation (ChIP) of wild-type EbfC showed it to bind in vivo to sites throughout the genome, two hallmarks of nucleoid-associated proteins. Comparative RNA sequencing (RNA-Seq) of a mutant B. burgdorferi strain that overexpresses EbfC indicated that approximately 4.5% of borrelial genes are significantly impacted by EbfC. The ebfC gene was highly expressed in rapidly growing bacteria, but ebfC mRNA was undetectable in stationary phase. Combined with previous data showing that EbfC induces bends in DNA, these results demonstrate that EbfC is a nucleoid-associated protein and lead to the hypothesis that B. burgdorferi utilizes cellular fluctuations in EbfC levels to globally control transcription of numerous genes. The ubiquity of EbfC proteins in Eubacteria suggests that these results apply to a wide range of pathogens and other bacteria.

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Preferential Presence of Decorin-Binding Protein B (BBA25) and BBA50 Antibodies in Cerebrospinal Fluid of Patients with Neurologic Lyme Disease

Cited by 10 publications

References 27 publications

Borrelia burgdorferi, Host-Derived Proteases, and the Blood-Brain Barrier

Borrelia burgdorferi, Host-Derived Proteases, and the Blood-Brain Barrier

Global Tn‐seq analysis of carbohydrate utilization and vertebrate infectivity of Borrelia burgdorferi

EbfC (YbaB) Is a New Type of Bacterial Nucleoid-Associated Protein and a Global Regulator of Gene Expression in the Lyme Disease Spirochete

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