scholarly journals Borrelia burgdorferi OspC Protein Required Exclusively in a Crucial Early Stage of Mammalian Infection

2006 ◽  
Vol 74 (6) ◽  
pp. 3554-3564 ◽  
Author(s):  
Kit Tilly ◽  
Jonathan G. Krum ◽  
Aaron Bestor ◽  
Mollie W. Jewett ◽  
Dorothee Grimm ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Salivary Glands ◽  
Early Stage ◽  
Natural Infection ◽  
Surface Protein ◽  
Mammalian Host ◽  
Infection Cycle ◽  
Persistently Infected ◽  
Tick Infection ◽  
Mammalian Infection

ABSTRACT This study demonstrates a strict temporal requirement for a virulence determinant of the Lyme disease spirochete Borrelia burgdorferi during a unique point in its natural infection cycle, which alternates between ticks and small mammals. OspC is a major surface protein produced by B. burgdorferi when infected ticks feed but whose synthesis decreases after transmission to a mammalian host. We have previously shown that spirochetes lacking OspC are competent to replicate in and migrate to the salivary glands of the tick vector but do not infect mice. Here we assessed the timing of the requirement for OspC by using an ospC mutant complemented with an unstable copy of the ospC gene and show that B. burgdorferi's requirement for OspC is specific to the mammal and limited to a critical early stage of mammalian infection. By using this unique system, we found that most bacterial reisolates from mice persistently infected with the initially complemented ospC mutant strain no longer carried the wild-type copy of ospC. Such spirochetes were acquired by feeding ticks and migrated to the tick salivary glands during subsequent feeding. Despite normal behavior in ticks, these ospC mutant spirochetes did not infect naive mice. ospC mutant spirochetes from persistently infected mice also failed to infect naive mice by tissue transplantation. We conclude that OspC is indispensable for establishing infection by B. burgdorferi in mammals but is not required at any other point of the mouse-tick infection cycle.

scholarly journals Borrelia burgdorferi Regulates Expression of Complement Regulator-Acquiring Surface Protein 1 during the Mammal-Tick Infection Cycle

2005 ◽  
Vol 73 (11) ◽  
pp. 7398-7405 ◽  
Author(s):  
Kate von Lackum ◽  
Jennifer C. Miller ◽  
Tomasz Bykowski ◽  
Sean P. Riley ◽  
Michael E. Woodman ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Immune Evasion ◽  
Expression Patterns ◽  
Surface Protein ◽  
Factor H ◽  
Complement Factor ◽  
Human Pathogens ◽  
Infection Cycle ◽  
Tick Infection ◽  
Complement Regulator

ABSTRACT During the natural mammal-tick infection cycle, the Lyme disease spirochete Borrelia burgdorferi comes into contact with components of the alternative complement pathway. B. burgdorferi, like many other human pathogens, has evolved the immune evasion strategy of binding two host-derived fluid-phase regulators of complement, factor H and factor H-like protein 1 (FHL-1). The borrelial complement regulator-acquiring surface protein 1 (CRASP-1) is a surface-exposed lipoprotein that binds both factor H and FHL-1. Analysis of CRASP-1 expression during the mammal-tick infectious cycle indicated that B. burgdorferi expresses this protein during mammalian infection, supporting the hypothesized role for CRASP-1 in immune evasion. However, CRASP-1 synthesis was repressed in bacteria during colonization of vector ticks. Analysis of cultured bacteria indicated that CRASP-1 is differentially expressed in response to changes in pH. Comparisons of CRASP-1 expression patterns with those of other infection-associated B. burgdorferi proteins, including the OspC, OspA, and Erp proteins, indicated that each protein is regulated through a unique mechanism.

scholarly journals Role of Borrelia burgdorferi Linear Plasmid 25 in Infection of Ixodes scapularis Ticks

2005 ◽  
Vol 187 (16) ◽  
pp. 5776-5781 ◽  
Author(s):  
Keith O. Strother ◽  
Aravinda de Silva
Keyword(s):  
Borrelia Burgdorferi ◽  
Genetic Manipulation ◽  
Natural Infection ◽  
Shuttle Vector ◽  
Linear Plasmid ◽  
Infection Prevalence ◽  
Infection Cycle ◽  
Tick Infection

ABSTRACT The tick-borne bacterium Borrelia burgdorferi has over 20 different circular and linear plasmids. Some B. burgdorferi plasmids are readily lost during in vitro culture or genetic manipulation. Linear plasmid 25, which is often lost in laboratory strains, is required for the infection of mice. Strains missing linear plasmid 25 (lp25−) are able to infect mice if the BBE22 gene on lp25 is provided on a shuttle vector. In this study, we examined the role of lp25 and BBE22 in tick infections. We tested the hypothesis that complementation with BBE22 in spirochetes lacking lp25 would restore the ability of spirochetes to infect ticks. A natural tick infection cycle was performed by feeding larvae on mice injected with the parental, lp25−, or lp25− BBE22-complemented spirochete strains. In addition, larvae and nymphs were artificially infected with different strains to study tick infections independent of mouse infections. B. burgdorferi missing lp25 was significantly impaired in its ability to infect larval and nymphal ticks. When an lp25− strain was complemented with BBE22, the ability to infect ticks was partially restored. Complementation with BBE22 allowed spirochetes lacking lp25 to establish short-term infections in ticks, but in most cases the infection prevalence was lower than that of the wild-type strain. In addition, the number of infected ticks decreased over time, suggesting that another gene(s) on lp25 is required for long-term persistence in ticks and completion of a natural infection cycle.

scholarly journals Delineating the Requirement for the Borrelia burgdorferi Virulence Factor OspC in the Mammalian Host

2006 ◽  
Vol 74 (6) ◽  
pp. 3547-3553 ◽  
Author(s):  
Philip E. Stewart ◽  
Xiaohui Wang ◽  
Dawn M. Bueschel ◽  
Dawn R. Clifton ◽  
Dorothee Grimm ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Physiological Role ◽  
Surface Protein ◽  
Protective Role ◽  
Innate Immune ◽  
Myeloid Differentiation ◽  
Mammalian Host ◽  
Mammalian Infection ◽  
Deficient Mice

ABSTRACT We previously demonstrated that outer surface protein C (OspC) of Borrelia burgdorferi is essential for establishing mammalian infection. However, the role of OspC in mammalian infection is unknown. Here, we report experiments designed to distinguish between two models of OspC function in the mammalian host: (i) OspC fulfills an essential physiological role for growth and host adaptation or (ii) OspC provides a protective role for evasion of components of the innate immune response. We found that a B. burgdorferi ospC mutant, previously demonstrated to be noninfectious in both immunocompetent and SCID mice, could survive in the relatively immune-privileged environment of dialysis membrane chambers implanted within the peritoneum of a rat. The ospC mutant also adapts to the mammalian environment, as determined by the protein profiles of the chamber-cultivated spirochetes. Therefore, OspC does not appear to provide a physiological function for the survival of B. burgdorferi within the mammalian host. The second model, evasion of the innate immune system, was tested by assessing the infectivity of the ospC mutant in mice deficient for myeloid differentiation protein 88 (MyD88). Recent studies have shown that B. burgdorferi is prevented from reaching high cell numbers in the mammalian host by MyD88-dependent signaling pathways. The ospC mutant was incapable of infecting MyD88-deficient mice, suggesting that the role of OspC cannot be related solely to evasion of MyD88-mediated innate immunity. These results reiterate the importance of OspC in mammalian infection and eliminate simple models of function for this enigmatic protein.

scholarly journals OspC-Independent Infection and Dissemination by Host-Adapted Borrelia burgdorferi

2009 ◽  
Vol 77 (7) ◽  
pp. 2672-2682 ◽  
Author(s):  
Kit Tilly ◽  
Aaron Bestor ◽  
Daniel P. Dulebohn ◽  
Patricia A. Rosa
Keyword(s):  
Borrelia Burgdorferi ◽  
Mouse Skin ◽  
Surface Protein ◽  
Mammalian Host ◽  
Recipient Mouse ◽  
Wild Type ◽  
Surface Protein Gene ◽  
Tick Transmission ◽  
Mammalian Infection

ABSTRACTBorrelia burgdorferiOspC is required for the spirochete to establish infection in a mammal by tick transmission or needle inoculation. After a brief essential period, the protein no longer is required and the gene can be shut off. Using a system in which spirochetes contain only an unstable wild-type copy of theospCgene, we can obtain mice persistently infected with bacteria lacking OspC. We implanted pieces of infected mouse skin subcutaneously in naïve mice, using donors carrying wild-type orospCmutant spirochetes, and found that both could infect mice by this method, with similar numbers of wild-type orospCmutant spirochetes disseminated throughout the tissues of recipient mice. Recipient mouse immune responses to tissue transfer-mediated infection with wild-type orospCmutant spirochetes were similar. These experiments demonstrate that mammalian host-adapted spirochetes can infect and disseminate in mice in the absence of OspC, thereby circumventing this hallmark of tick-derived or in vitro-grown spirochetes. We propose a model in which OspC is one of a succession of functionally equivalent, essential proteins that are synthesized at different stages of mammalian infection. In this model, another protein uniquely present on host-adapted spirochetes performs the same essential function initially fulfilled by OspC. The strict temporal control ofB. burgdorferiouter surface protein gene expression may reflect immunological constraints rather than distinct functions.

scholarly journals Borrelia burgdorferi RevA Antigen Binds Host Fibronectin

2009 ◽  
Vol 77 (7) ◽  
pp. 2802-2812 ◽  
Author(s):  
Catherine A. Brissette ◽  
Tomasz Bykowski ◽  
Anne E. Cooley ◽  
Amy Bowman ◽  
Brian Stevenson
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Surface Protein ◽  
Site Directed Mutagenesis ◽  
Heparin Binding ◽  
Amino Terminal ◽  
Ligand Interactions ◽  
Fibronectin Binding Protein ◽  
Vertebrate Hosts ◽  
Mammalian Infection

ABSTRACT Borrelia burgdorferi, the Lyme disease-causing spirochete, can persistently infect its vertebrate hosts for years. B. burgdorferi is often found associated with host connective tissue, where it interacts with components of the extracellular matrix, including fibronectin. Some years ago, a borrelial surface protein, named BBK32, was identified as a fibronectin-binding protein. However, B. burgdorferi BBK32 mutants are still able to bind fibronectin, indicating that the spirochete possesses additional mechanisms for adherence to fibronectin. We now demonstrate that RevA, an unrelated B. burgdorferi outer surface protein, binds mammalian fibronectin in a saturable manner. Site-directed mutagenesis studies identified the amino terminus of the RevA protein as being required for adhesion to fibronectin. RevA bound to the amino-terminal region of fibronectin. RevA binding to fibronectin was not inhibited by salt or heparin, suggesting that adhesin-ligand interactions are primarily nonionic and occur through the non-heparin-binding regions of the fibronectin amino-terminal domains. revA genes are widely distributed among Lyme disease spirochetes, and the present studies determined that all RevA alleles tested bound fibronectin. In addition, RevB, a paralogous protein found in a subset of B. burgdorferi strains, also bound fibronectin. We also confirmed that RevA is produced during mammalian infection but not during colonization of vector ticks and determined that revA transcription is controlled through a mechanism distinct from that of BBK32.

scholarly journals Outer Surface Protein C Is a Dissemination-Facilitating Factor of Borrelia burgdorferi during Mammalian Infection

PLoS ONE ◽  
2010 ◽  
Vol 5 (12) ◽  
pp. e15830 ◽  
Author(s):  
Sunita V. Seemanapalli ◽  
Qilong Xu ◽  
Kristy McShan ◽  
Fang Ting Liang
Keyword(s):  
Borrelia Burgdorferi ◽  
Outer Surface ◽  
Protein C ◽  
Surface Protein ◽  
Outer Surface Protein ◽  
Mammalian Infection

scholarly journals Evaluation of RevA, a Fibronectin-Binding Protein of Borrelia burgdorferi, as a Potential Vaccine Candidate for Lyme Disease

2013 ◽  
Vol 20 (6) ◽  
pp. 892-899 ◽  
Author(s):  
Angela M. Floden ◽  
Tammy Gonzalez ◽  
Robert A. Gaultney ◽  
Catherine A. Brissette
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Passive Immunization ◽  
Surface Protein ◽  
Surface Expression ◽  
Content Type ◽  
Good Target ◽  
Potential Vaccine ◽  
Mammalian Infection

ABSTRACTPrevious studies indicated that the Lyme disease spirocheteBorrelia burgdorferiexpresses the RevA outer surface protein during mammalian infection. As an adhesin that promotes bacterial interaction with fibronectin, RevA appears to be a good target for preventive therapies. RevA proteins are highly conserved across all Lyme borreliae, and antibodies against RevA protein are cross-reactive among RevA proteins from diverse strains. Mice infected withB. burgdorferimounted a rapid IgM response to RevA, followed by a strong IgG response that generally remained elevated for more than 12 months, suggesting continued exposure of RevA protein to the immune system. RevA antibodies were bactericidalin vitro. To evaluate the RevA antigen as a potential vaccine, mice were vaccinated with recombinant RevA and challenged withB. burgdorferiby inoculation with a needle or by a tick bite. Cultured tissues from all treatment groups were positive forB. burgdorferi. Vaccinated animals also appeared to have similar levels ofB. burgdorferiDNA compared to nonvaccinated controls. Despite its antigenicity, surface expression, and the production of bactericidal antibodies against it, RevA does not protect againstBorrelia burgdorferiinfection in a mouse model. However, passive immunization with anti-RevA antibodies did prevent infection, suggesting the possible utility of RevA-based immunotherapeutics or vaccine.

scholarly journals Changes in Temporal and Spatial Patterns of Outer Surface Lipoprotein Expression Generate Population Heterogeneity and Antigenic Diversity in the Lyme Disease Spirochete, Borrelia burgdorferi

2002 ◽  
Vol 70 (7) ◽  
pp. 3468-3478 ◽  
Author(s):  
P. Scott Hefty ◽  
Sarah E. Jolliff ◽  
Melissa J. Caimano ◽  
Stephen K. Wikel ◽  
Darrin R. Akins
Keyword(s):  
Borrelia Burgdorferi ◽  
Salivary Glands ◽  
Cellular Localization ◽  
Expression Patterns ◽  
Population Heterogeneity ◽  
Mammalian Host ◽  
Tick Feeding ◽  
Temporal And Spatial ◽  
Cultivation In Vitro

ABSTRACT Borrelia burgdorferi differentially expresses many of the OspE/F/Elp paralogs during tick feeding. These findings, combined with the recent report that stable B. burgdorferi infection of mammals occurs only after 53 h of tick attachment, prompted us to further analyze the expression of the OspE/F/Elp paralogs during this critical period of transmission. Indirect immunofluorescence analysis revealed that OspE, p21, ElpB1, ElpB2, and OspF/BbK2.11 are expressed in the salivary glands of ticks allowed to feed on mice for 53 to 58 h. Interestingly, many of the spirochetes in the salivary glands that expressed abundant amounts of these antigens were negative for OspA and OspC. Although prior reports have indicated that OspE/F/Elp orthologs are surface exposed, none of the individual lipoproteins or combinations of the lipoproteins protected mice from challenge infections. To examine why these apparently surface-exposed lipoproteins were not protective, we analyzed their genetic stability during infection and their cellular locations after cultivation in vitro and within dialysis membrane chambers, mimicking a mammalian host-adapted state. Combined restriction fragment length polymorphism and nucleotide sequence analyses revealed that the genes encoding these lipoproteins are stable for at least 8 months postinfection. Interestingly, cellular localization experiments revealed that while all of these proteins can be surface localized, there were significant populations of spirochetes that expressed these lipoproteins only in the periplasm. Furthermore, host-specific signals were found to alter the expression patterns and final cellular location of these lipoproteins. The combined data revealed a remarkable heterogeneity in populations of B. burgdorferi during tick transmission and mammalian infection. The diversity is generated not only by temporal changes in antigen expression but also by modulation of the surface lipoproteins during infection. The ability to regulate the temporal and spatial expression patterns of lipoproteins throughout infection likely contributes to persistent infection of mammals by B. burgdorferi.

scholarly journals Borrelia burgdorferi complement regulator-acquiring surface proteins (BbCRASPs): Expression patterns during the mammal–tick infection cycle

2008 ◽  
Vol 298 ◽  
pp. 249-256 ◽  
Author(s):  
Tomasz Bykowski ◽  
Michael E. Woodman ◽  
Anne E. Cooley ◽  
Catherine A. Brissette ◽  
Reinhard Wallich ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Expression Patterns ◽  
Surface Proteins ◽  
Infection Cycle ◽  
Tick Infection ◽  
Complement Regulator

scholarly journals Specific Expression of Anaplasma marginale Major Surface Protein 2 Salivary Gland Variants Occurs in the Midgut and Is an Early Event during Tick Transmission

2002 ◽  
Vol 70 (1) ◽  
pp. 114-120 ◽  
Author(s):  
Christiane V. Löhr ◽  
Fred R. Rurangirwa ◽  
Terry F. McElwain ◽  
David Stiller ◽  
Guy H. Palmer
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Surface Protein ◽  
Anaplasma Marginale ◽  
Mammalian Host ◽  
Early Event ◽  
Variant Selection ◽  
Specific Expression ◽  
Major Surface Protein ◽  
Major Surface

ABSTRACT Infectivity of Anaplasma spp. develops when infected ticks feed on a mammalian host (transmission feed). Specific Anaplasma marginale major surface protein 2 (MSP2) variants are selected for within the tick and are expressed within the salivary glands. The aims of this study were to determine when and where MSP2 variant selection occurs in the tick, how MSP2 expression is regulated in salivary glands of transmission-feeding ticks, and whether the number of A. marginale organisms per salivary gland is significantly increased during transmission feeding. The South Idaho strain of A. marginale was used, as MSP2 expression is restricted to two variants, SGV1 and SGV2, in Dermacentor andersoni. Using Western blot, real-time PCR, and DNA sequencing analyses it was shown that restriction and expression of MSP2 occurs early in the midgut within the first 48 h of the blood meal, when ticks acquire infection. A. marginale is present in the tick salivary glands before transmission feeding is initiated, but the msp2 mRNA and MSP2 protein levels per A. marginale organism increase only minimally and transiently in salivary glands of transmission-feeding ticks compared to that of unfed ticks. A. marginale numbers per tick increase gradually in salivary glands of both transmission-fed and unfed ticks. It is concluded that MSP2 variant selection is an early event in the tick and that MSP2 variants SGV1 and SGV2 are expressed both in the midgut and salivary glands. While MSP2 may be required for infectivity, there is no strict temporal correlation between MSP2 expression and the development of infectivity.

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