scholarly journals Borrelia burgdorferi Surface Exposed GroEL Is a Multifunctional Protein

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 226
Author(s):  
Thomas Cafiero ◽  
Alvaro Toledo
Keyword(s):  
Borrelia Burgdorferi ◽  
Outer Membrane ◽  
Complex Life Cycle ◽  
Mammalian Host ◽  
Dependent Manner ◽  
Rabbit Antibody ◽  
Multifunctional Protein ◽  
Tick Vector ◽  
Chaperone Protein ◽  
His Tag

The spirochete, Borrelia burgdorferi, has a large number of membrane proteins involved in a complex life cycle, that includes a tick vector and a vertebrate host. Some of these proteins also serve different roles in infection and dissemination of the spirochete in the mammalian host. In this spirochete, a number of proteins have been associated with binding to plasminogen or components of the extracellular matrix, which is important for tissue colonization and dissemination. GroEL is a cytoplasmic chaperone protein that has previously been associated with the outer membrane of Borrelia. A His-tag purified B. burgdorferi GroEL was used to generate a polyclonal rabbit antibody showing that GroEL also localizes in the outer membrane and is surface exposed. GroEL binds plasminogen in a lysine dependent manner. GroEL may be part of the protein repertoire that Borrelia successfully uses to establish infection and disseminate in the host. Importantly, this chaperone is readily recognized by sera from experimentally infected mice and rabbits. In summary, GroEL is an immunogenic protein that in addition to its chaperon role it may contribute to pathogenesis of the spirochete by binding to plasminogen and components of the extra cellular matrix.

scholarly journals Borrelia burgdorferi Alters Its Gene Expression and Antigenic Profile in Response to CO2 Levels

2006 ◽  
Vol 189 (2) ◽  
pp. 437-445 ◽  
Author(s):  
Jenny A. Hyde ◽  
Jerome P. Trzeciakowski ◽  
Jonathan T. Skare
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Borrelia Burgdorferi ◽  
Growth Conditions ◽  
Etiologic Agent ◽  
Complex Life Cycle ◽  
Mammalian Host ◽  
Transcriptional Level ◽  
Virulence Determinants

ABSTRACT The etiologic agent of Lyme disease, Borrelia burgdorferi, must adapt to the distinct environments of its arthropod vector and mammalian host during its complex life cycle. B. burgdorferi alters gene expression and protein synthesis in response to temperature, pH, and other uncharacterized environmental factors. The hypothesis tested in this study is that dissolved gases, including CO2, serve as a signal for B. burgdorferi to alter protein production and gene expression. In this study we focused on characterization of in vitro anaerobic (5% CO2, 3% H2, 0.087 ppm O2) and microaerophilic (1% CO2, 3.48 ppm O2) growth conditions and how they modulate protein synthesis and gene expression in B. burgdorferi. Higher levels of several immunoreactive proteins, including BosR, NapA, DbpA, OspC, BBK32, and RpoS, were synthesized under anaerobic conditions. Previous studies demonstrated that lower levels of NapA were produced when microaerophilic cultures were purged with nitrogen gas to displace oxygen and CO2. In this study we identified CO2 as a factor contributing to the observed change in NapA synthesis. Specifically, a reduction in the level of dissolved CO2, independent of O2 levels, resulted in reduced NapA synthesis. BosR, DbpA, OspC, and RpoS synthesis was also decreased with the displacement of CO2. Quantitative reverse transcription-PCR indicated that the levels of the dbpA, ospC, and BBK32 transcripts are increased in the presence of CO2, indicating that these putative borrelial virulence determinants are regulated at the transcriptional level. Thus, dissolved CO2 may be an additional cue for borrelial host adaptation and gene regulation.

scholarly journals DhhP, a Cyclic di-AMP Phosphodiesterase of Borrelia burgdorferi, Is Essential for Cell Growth and Virulence

2014 ◽  
Vol 82 (5) ◽  
pp. 1840-1849 ◽  
Author(s):  
Meiping Ye ◽  
Jun-Jie Zhang ◽  
Xin Fang ◽  
Gavin B. Lawlis ◽  
Bryan Troxell ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Wild Type Strain ◽  
Wall Structure ◽  
Mammalian Host ◽  
Dependent Manner ◽  
Gram Positive ◽  
Content Type ◽  
Gram Positive Bacteria

ABSTRACTCyclic di-AMP (c-di-AMP) is a recently discovered second messenger in bacteria. Most of work on c-di-AMP signaling has been done in Gram-positive bacteria, firmicutes, and actinobacteria, where c-di-AMP signaling pathways affect potassium transport, cell wall structure, and antibiotic resistance. Little is known about c-di-AMP signaling in other bacteria.Borrelia burgdorferi, the causative agent of Lyme disease, is a spirochete that has a Gram-negative dual membrane. In this study, we demonstrated thatB. burgdorferiBB0619, aDHH-DHHA1 domainprotein (herein designated DhhP), functions as c-di-AMP phosphodiesterase. Recombinant DhhP hydrolyzed c-di-AMP to pApA in a Mn2+- or Mg2+-dependent manner. In contrast to c-di-AMP phosphodiesterases reported thus far, DhhP appears to be essential forB. burgdorferigrowth bothin vitroand in the mammalian host. Inactivation of the chromosomaldhhPgene could be achieved only in the presence of a plasmid-encoded inducibledhhPgene. The conditionaldhhPmutant had a dramatic increase in intracellular c-di-AMP level in comparison to the isogenic wild-type strain. Unlike what has been observed in Gram-positive bacteria, elevated cellular c-di-AMP inB. burgdorferidid not result in an increased resistance to β-lactamase antibiotics, suggesting that c-di-AMP's functions in spirochetes differ from those in Gram-positive bacteria. In addition, thedhhPmutant was defective in induction of the σSfactor, RpoS, and the RpoS-dependent outer membrane virulence factor OspC, which uncovers an important role of c-di-AMP inB. burgdorferivirulence.

scholarly journals Structural and Functional Analysis of BBA03, Borrelia burgdorferi Competitive Advantage Promoting Outer Surface Lipoprotein

Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 826
Author(s):  
Jēkabs Fridmanis ◽  
Raitis Bobrovs ◽  
Kalvis Brangulis ◽  
Kaspars Tārs ◽  
Kristaps Jaudzems
Keyword(s):  
Borrelia Burgdorferi ◽  
Competitive Advantage ◽  
Outer Surface ◽  
Solution Nmr ◽  
Mammalian Host ◽  
Tick Vector ◽  
Evolutionary Relatedness ◽  
Relatedness Analysis ◽  
Linear Plasmid 54

BBA03 is a Borrelia burgdorferi outer surface lipoprotein encoded on one of the most conserved plasmids in Borrelia genome, linear plasmid 54 (lp54). Although many of its genes have been identified as contributing or essential for spirochete fitness in vivo, the majority of the proteins encoded on this plasmid have no known function and lack homologs in other organisms. In this paper, we report the solution NMR structure of the B. burgdorferi outer surface lipoprotein BBA03, which is known to provide a competitive advantage to the bacteria during the transmission from tick vector to mammalian host. BBA03 shows structural homology to other outer surface lipoproteins reflecting their genetic and evolutionary relatedness. Analysis of the structure reveals a pore in BBA03, which could potentially bind lipids.

scholarly journals Reptile Host Associations of Ixodes scapularis in Florida and Implications for Borrelia spp. Ecology

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 999
Author(s):  
Carrie De Jesus ◽  
Chanakya Bhosale ◽  
Kristen Wilson ◽  
Zoe White ◽  
Samantha M. Wisely
Keyword(s):  
Borrelia Burgdorferi ◽  
Ixodes Scapularis ◽  
Borrelia Burgdorferi Sensu Lato ◽  
Mammalian Host ◽  
Lizard Species ◽  
Tissue Samples ◽  
Tick Vector ◽  
Reservoir Species ◽  
Drift Fence ◽  
Host Associations

Host associations of the tick vector for Lyme Borreliosis, Ixodes scapularis, differ across its geographic range. In Florida, the primary competent mammalian host of Lyme disease is not present but instead has other small mammals and herpetofauna that I. scapularis can utilize. We investigated host–tick association for lizards, the abundance of ticks on lizards and the prevalence of Borrelia burgdorferi sensu lato (sl). To determine which lizard species I. scapularis associates with, we examined 11 native lizard species from historical herpetological specimens. We found that (294/5828) of the specimens had attached ticks. The most infested species were Plestiodon skinks (241/1228) and Ophisaurus glass lizards (25/572). These species were then targeted at six field sites across Florida and sampled from June to September 2020, using drift fence arrays, cover boards and fishing. We captured 125 lizards and collected 233 immature I. scapularis. DNA was extracted from ticks and lizard tissue samples, followed by PCR testing for Borrelia spp. Of the captured lizards, 69/125 were infested with immature I. scapularis. We did not detect Borrelia spp. from tick or lizard tissue samples. Overall, we found that lizards are commonly infested with I. scapularis. However, we did not detect Borrelia burgdorferi sl. These findings add to a growing body of evidence that lizards are poor reservoir species.

scholarly journals The Enolase of Borrelia burgdorferi Is a Plasminogen Receptor Released in Outer Membrane Vesicles

2011 ◽  
Vol 80 (1) ◽  
pp. 359-368 ◽  
Author(s):  
A. Toledo ◽  
J. L. Coleman ◽  
C. J. Kuhlow ◽  
J. T. Crowley ◽  
J. L. Benach
Keyword(s):  
Lyme Disease ◽  
Membrane Proteins ◽  
Borrelia Burgdorferi ◽  
Outer Membrane ◽  
Outer Membrane Proteins ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Proteinase K ◽  
Dependent Manner ◽  
Content Type

ABSTRACTThe agent of Lyme disease,Borrelia burgdorferi, has a number of outer membrane proteins that are differentially regulated during its life cycle. In addition to their physiological functions in the organism, these proteins also likely serve different functions in invasiveness and immune evasion. In borreliae, as well as in other bacteria, a number of membrane proteins have been implicated in binding plasminogen. The activation and transformation of plasminogen into its proteolytically active form, plasmin, enhances the ability of the bacteria to disseminate in the host. Outer membrane vesicles ofB. burgdorfericontain enolase, a glycolytic-cycle enzyme that catalyzes 2-phosphoglycerate to form phosphoenolpyruvate, which is also a known plasminogen receptor in Gram-positive bacteria. The enolase was cloned, expressed, purified, and used to generate rabbit antienolase serum. The enolase binds plasminogen in a lysine-dependent manner but not through ionic interactions. Although it is present in the outer membrane, microscopy and proteinase K treatment showed that enolase does not appear to be exposed on the surface. However, enolase in the outer membrane vesicles is accessible to proteolytic degradation by proteinase K. Samples from experimentally and tick-infected mice and rabbits as well as from Lyme disease patients exhibit recognition of enolase in serologic assays. Thus, this immunogenic plasminogen receptor released in outer membrane vesicles could be responsible for external proteolysis in the pericellular environment and have roles in nutrition and in enhancing dissemination.

scholarly journals PlzA is a bifunctional c-di-GMP biosensor that promotes tick and mammalian host-adaptation of Borrelia burgdorferi

2021 ◽  
Vol 17 (7) ◽  
pp. e1009725
Author(s):  
Ashley M. Groshong ◽  
André A. Grassmann ◽  
Amit Luthra ◽  
Melissa A. McLain ◽  
Anthony A. Provatas ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Conformational Changes ◽  
Host Adaptation ◽  
Mammalian Host ◽  
Dependent Manner ◽  
Independent Function ◽  
Protective Function ◽  
Saxs Analysis ◽  
Immunocompetent Mice

In this study, we examined the relationship between c-di-GMP and its only known effector protein, PlzA, in Borrelia burgdorferi during the arthropod and mammalian phases of the enzootic cycle. Using a B. burgdorferi strain expressing a plzA point mutant (plzA-R145D) unable to bind c-di-GMP, we confirmed that the protective function of PlzA in ticks is c-di-GMP-dependent. Unlike ΔplzA spirochetes, which are severely attenuated in mice, the plzA-R145D strain was fully infectious, firmly establishing that PlzA serves a c-di-GMP-independent function in mammals. Contrary to prior reports, loss of PlzA did not affect expression of RpoS or RpoS-dependent genes, which are essential for transmission, mammalian host-adaptation and murine infection. To ascertain the nature of PlzA’s c-di-GMP-independent function(s), we employed infection models using (i) host-adapted mutant spirochetes for needle inoculation of immunocompetent mice and (ii) infection of scid mice with in vitro-grown organisms. Both approaches substantially restored ΔplzA infectivity, suggesting that PlzA enables B. burgdorferi to overcome an early bottleneck to infection. Furthermore, using a Borrelia strain expressing a heterologous, constitutively active diguanylate cyclase, we demonstrate that ‘ectopic’ production of c-di-GMP in mammals abrogates spirochete virulence and interferes with RpoS function at the post-translational level in a PlzA-dependent manner. Structural modeling and SAXS analysis of liganded- and unliganded-PlzA revealed marked conformational changes that underlie its biphasic functionality. This structural plasticity likely enables PlzA to serve as a c-di-GMP biosensor that in its respective liganded and unliganded states promote vector- and host-adaptation by the Lyme disease spirochete.

scholarly journals Borrelia burgdorferi bba66Gene Inactivation Results in Attenuated Mouse Infection by Tick Transmission

2013 ◽  
Vol 81 (7) ◽  
pp. 2488-2498 ◽  
Author(s):  
Toni G. Patton ◽  
Kevin S. Brandt ◽  
Christi Nolder ◽  
Dawn R. Clifton ◽  
James A. Carroll ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Ixodes Scapularis ◽  
Disease Process ◽  
Mammalian Host ◽  
Content Type ◽  
Tick Vector ◽  
Tick Transmission ◽  
Encoding Gene ◽  
Host Infection ◽  
The Impact

ABSTRACTThe impact of theBorrelia burgdorferisurface-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-tick-mouse cycle. The BBA66-deficient mutant isolate, BbΔA66, 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 scapularislarvae successfully acquired BbΔA66following 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 BbΔA66-infected nymphs to infect laboratory mice was significantly impaired compared to that of mice fed upon by WT-infected ticks.trans-complementation of BbΔA66with an intact copy ofbba66restored the WT infectious phenotype in mice via tick transmission. These results suggest a role for BBA66 in facilitatingB. burgdorferidissemination and transmission from the tick vector to the mammalian host as part of the disease process for Lyme borreliosis.

Effects of cytochrome c on the mitochondrial apoptosis-induced channel MAC

2004 ◽  
Vol 286 (5) ◽  
pp. C1109-C1117 ◽  
Author(s):  
Liang Guo ◽  
Dawn Pietkiewicz ◽  
Evgeny V. Pavlov ◽  
Sergey M. Grigoriev ◽  
John J. Kasianowicz ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Outer Membrane ◽  
Cell Types ◽  
Rnase A ◽  
Mitochondrial Outer Membrane ◽  
Dependent Manner ◽  
Mitochondrial Apoptosis ◽  
Noise Type ◽  
Voltage Dependent

Recent studies indicate that cytochrome c is released early in apoptosis without loss of integrity of the mitochondrial outer membrane in some cell types. The high-conductance mitochondrial apoptosis-induced channel (MAC) forms in the outer membrane early in apoptosis of FL5.12 cells. Physiological (micromolar) levels of cytochrome c alter MAC activity, and these effects are referred to as types 1 and 2. Type 1 effects are consistent with a partitioning of cytochrome c into the pore of MAC and include a modest decrease in conductance that is dose and voltage dependent, reversible, and has an increase in noise. Type 2 effects may correspond to “plugging” of the pore or destabilization of the open state. Type 2 effects are a dose-dependent, voltage-independent, and irreversible decrease in conductance. MAC is a heterogeneous channel with variable conductance. Cytochrome c affects MAC in a pore size-dependent manner, with maximal effects of cytochrome c on MAC with conductance of 1.9–5.4 nS. The effects of cytochrome c, RNase A, and high salt on MAC indicate that size, rather than charge, is crucial. The effects of dextran molecules of various sizes indicate that the pore diameter of MAC is slightly larger than that of 17-kDa dextran, which should be sufficient to allow the passage of 12-kDa cytochrome c. These findings are consistent with the notion that MAC is the pore through which cytochrome c is released from mitochondria during apoptosis.

Defining Plasmids Required by Borrelia burgdorferi for Colonization of Tick Vector Ixodes scapularis (Acari: Ixodidae)

2005 ◽  
Vol 42 (4) ◽  
pp. 676-684 ◽  
Author(s):  
Dorothee Grimm ◽  
Kit Tilly ◽  
Dawn M. Bueschel ◽  
Mark A. Fisher ◽  
Paul F. Policastro ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Ixodes Scapularis ◽  
Tick Vector

scholarly journals Borrelia burgdorferi Lacking BBK32, a Fibronectin-Binding Protein, Retains Full Pathogenicity

2006 ◽  
Vol 74 (6) ◽  
pp. 3305-3313 ◽  
Author(s):  
Xin Li ◽  
Xianzhong Liu ◽  
Deborah S. Beck ◽  
Fred S. Kantor ◽  
Erol Fikrig
Keyword(s):  
Life Cycle ◽  
Borrelia Burgdorferi ◽  
Deletion Mutant ◽  
Binding Protein ◽  
Kanamycin Resistance ◽  
Binding Activity ◽  
Mammalian Host ◽  
Wild Type ◽  
Fibronectin Binding Protein ◽  
Fibronectin Binding

ABSTRACT BBK32, a fibronectin-binding protein of Borrelia burgdorferi, is one of many surface lipoproteins that are differentially expressed by the Lyme disease spirochete at various stages of its life cycle. The level of BBK32 expression in B. burgdorferi is highest during infection of the mammalian host and lowest in flat ticks. This temporal expression profile, along with its fibronectin-binding activity, strongly suggests that BBK32 may play an important role in Lyme pathogenesis in the host. To test this hypothesis, we constructed an isogenic BBK32 deletion mutant from wild-type B. burgdorferi B31 by replacing the BBK32 gene with a kanamycin resistance cassette through homologous recombination. We examined both the wild-type strain and the BBK32 deletion mutant extensively in the experimental mouse-tick model of the Borrelia life cycle. Our data indicated that B. burgdorferi lacking BBK32 retained full pathogenicity in mice, regardless of whether mice were infected artificially by syringe inoculation or naturally by tick bite. The loss of BBK32 expression in the mutant had no adverse effect on spirochete acquisition (mouse-to-tick) and transmission (tick-to-mouse) processes. These results suggest that additional B. burgdorferi proteins can complement the function of BBK32, fibronectin binding or otherwise, during the natural spirochete life cycle.

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