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 Role of the BBA64 Locus of Borrelia burgdorferi in Early Stages of Infectivity in a Murine Model of Lyme Disease

2007 ◽  
Vol 76 (1) ◽  
pp. 391-402 ◽  
Author(s):  
Mahulena Maruskova ◽  
M. Dolores Esteve-Gassent ◽  
Valerie L. Sexton ◽  
J. Seshu
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Immunoblot Analysis ◽  
Open Reading Frames ◽  
Mammalian Host ◽  
Environmental Signals ◽  
Significant Difference ◽  
Linear Plasmid 54

ABSTRACT Borrelia burgdorferi, the causative agent of Lyme disease, undergoes rapid adaptive gene expression in response to environmental signals encountered during different stages of its life cycle in the arthropod vector or the mammalian host. Among all the plasmid-encoded genes of B. burgdorferi, several linear plasmid 54 (lp54)-encoded open reading frames (ORFs) exhibit the greatest differential expression in response to mammalian host-specific temperature, pH, and other uncharacterized signals. These ORFs include members of the paralogous gene family 54 (pgf 54), such as BBA64, BBA65, and BBA66, present on lp54. In an attempt to correlate transcriptional up-regulation of these pgf 54 members to their role in infectivity, we inactivated BBA64 and characterized the phenotype of this mutant both in vitro and in vivo. There were no major differences in the protein profiles between the BBA64 mutant and the control strains, while immunoblot analysis indicated that inactivation of BBA64 resulted in increased levels of BBA65. Moreover, there was no significant difference in the ability of the BBA64 mutant to infect C3H/HeN mice compared to that of its parental or complemented control strains as determined by culturing of viable spirochetes from infected tissues. However, enumeration of spirochetes using quantitative real-time PCR revealed tissue-specific differences, suggesting a minimal role for BBA64 in the survival of B. burgdorferi in select tissues. Infectivity analysis of the BBA64 mutant suggests that B. burgdorferi may utilize multiple determinants to establish infection in mammalian hosts.

scholarly journals The Failure of Immune Response Evasion by Linear Plasmid 28-1-Deficient Borrelia burgdorferi Is Attributable to Persistent Expression of an Outer Surface Protein

2008 ◽  
Vol 76 (9) ◽  
pp. 3984-3991 ◽  
Author(s):  
Monica E. Embers ◽  
Xavier Alvarez ◽  
Tara Ooms ◽  
Mario T. Philipp
Keyword(s):  
Immune Response ◽  
Borrelia Burgdorferi ◽  
Outer Surface ◽  
Time Course ◽  
Surface Protein ◽  
Etiologic Agent ◽  
Linear Plasmid ◽  
Mammalian Host ◽  
Outer Surface Protein

ABSTRACT Infectivity and persistence by Borrelia burgdorferi, the etiologic agent of Lyme disease, rely stringently on regulatory events. Among these is the downregulation of lipoprotein antigen expression, exemplified by outer surface protein C (OspC), at the advent of specific immunity in the mammalian host. B. burgdorferi spirochetes that lack the linear plasmid 28-1 (lp28-1) succumb to the host's immune response. We thus explored the notion that these two phenomena were related—that lp28-1− organisms fail to downregulate ospC and thus are cleared following the appearance of anti-OspC antibody in the murine host. The lp-28-1− isolate and a wild-type (wt) isolate bearing the complete set of plasmids were grown in dialysis membrane chambers that were implanted into rat peritoneal cavities. Analysis of mRNA and protein from these cultures showed that OspC expression levels by lp28-1− organisms are abnormally high in vivo. A time course analysis of ospC expression in tissues following infection indicates also that temporal diminution of the dominant antigen OspC is impaired in lp28-1− spirochetes. Finally, passive transfer of monoclonal OspC-specific antibody into SCID mice 8 days postinfection cleared lp28-1− spirochetes, yet the wt organisms persisted in a majority of animals. These findings indicate that incomplete repression of OspC by lp28-1− organisms renders them susceptible to immune-mediated clearance. The lp28-1 plasmid must harbor one or more genes involved in OspC downregulation.

scholarly journals Does Host Complement Kill Borrelia burgdorferi within Ticks?

2003 ◽  
Vol 71 (2) ◽  
pp. 822-829 ◽  
Author(s):  
Sivaprakash Rathinavelu ◽  
Anne Broadwater ◽  
Aravinda M. de Silva
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Outer Surface ◽  
Protein A ◽  
Surface Protein ◽  
Block Transmission ◽  
Outer Surface Protein A ◽  
Tick Vector ◽  
Host Blood ◽  
Transmission Blocking Vaccine

ABSTRACT The Lyme disease spirochete, Borrelia burgdorferi, inhabits the gut lumen of the tick vector. At this location the spirochete is exposed to host blood when a tick feeds. We report here on studies that were done with normal and complement-deficient (C3-knockout) mice to determine if the host complement system killed spirochetes within the vector. We found that spirochete numbers within feeding nymphs were not influenced by complement, most likely because host complement was inactivated within the vector. The Lyme disease outer surface protein A (OspA) vaccine is a transmission-blocking vaccine that targets spirochetes in the vector. In experiments with mice hyperimmunized with OspA, complement was not required to kill spirochetes within nymphs and to block transmission from nymphs to the vaccinated host. However, host complement did enhance the ability of OspA antibody to block larvae from acquiring spirochetes. Thus, the effects of OspA antibody on nymphal transmission and larval acquisition appear to be based on different mechanisms.

scholarly journals Alternate Sigma Factor RpoS Is Required for the In Vivo-Specific Repression of Borrelia burgdorferi Plasmid lp54-Borne ospA and lp6.6 Genes

2005 ◽  
Vol 187 (22) ◽  
pp. 7845-7852 ◽  
Author(s):  
Melissa J. Caimano ◽  
Christian H. Eggers ◽  
Cynthia A. Gonzalez ◽  
Justin D. Radolf
Keyword(s):  
Borrelia Burgdorferi ◽  
Sigma Factor ◽  
Mammalian Host ◽  
Alternative Sigma Factor ◽  
Tick Feeding ◽  
Accessory Factor ◽  
Repressor Molecule ◽  
Specific Virulence ◽  
Sigma Factor Rpos

ABSTRACT While numerous positively regulated loci have been characterized during the enzootic cycle of Borrelia burgdorferi, very little is known about the mechanism(s) involved in the repression of borrelial loci either during tick feeding or within the mammalian host. Here, we report that the alternative sigma factor RpoS is required for the in vivo-specific repression of at least two RpoD-dependent B. burgdorferi loci, ospA and lp6.6. The downregulation of ospA and Ip6.6 appears to require either a repressor molecule whose expression is RpoS dependent or an accessory factor which enables RpoS to directly interact with the ospA and Ip6.6 promoter elements, thereby blocking transcription by RpoD. The central role for RpoS during the earliest stages of host adaptation suggests that tick feeding imparts signals to spirochetes that trigger the RpoS-dependent repression, as well as expression, of in vivo-specific virulence factors critical for the tick-to-mammalian host transition.

scholarly journals Host-Adapted Borrelia burgdorferi in Mice Expresses OspA during Inflammation

2003 ◽  
Vol 71 (7) ◽  
pp. 4003-4010 ◽  
Author(s):  
Helena Crowley ◽  
Brigitte T. Huber
Keyword(s):  
Borrelia Burgdorferi ◽  
Protein A ◽  
Surface Protein ◽  
Conclusive Evidence ◽  
Antibody Responses ◽  
In Vivo Model ◽  
Mammalian Host ◽  
Outer Surface Protein A ◽  
Reverse Transcription Pcr

ABSTRACT Antibody responses to outer surface protein A (OspA) of Borrelia burgdorferi may occur during periods of arthritis late in the clinical course of untreated Lyme disease. These antibody responses are paradoxical, given the conclusive evidence demonstrating that B. burgdorferi transmitted to the mammalian host expresses little or no OspA. The parallel occurrence of OspA antibodies and arthritic episodes suggests that OspA expression is upregulated during infection with B. burgdorferi. We hypothesized that this was due to the inflammatory environment caused by the immune response to the spirochete. To test our hypothesis, we adapted an in vivo model that mimics the host-pathogen interaction. Dialysis chambers containing B. burgdorferi were implanted into the peritoneal cavities of mice in the presence or absence of zymosan, a yeast cell wall extract that induces inflammation. Spirochetes were harvested 2 days later, and OspA expression was assessed at the protein and transcription level by Western blotting and real-time reverse transcription-PCR, respectively. Flow cytometry was also utilized to evaluate OspA protein expression on individual spirochetes. B. burgdorferi maintained in an inflammatory in vivo environment show an increased OspA expression relative to B. burgdorferi kept under normal in vivo conditions. Furthermore, host-adapted B. burgdorferi with a low OspA phenotype upregulates OspA expression when transferred to an inflammatory in vivo environment. The results obtained by these techniques uniformly identify inflammation as a mediator of in vivo OspA expression in host-adapted B. burgdorferi, providing insights into the behavior of live spirochetes in the mammalian host.

scholarly journals Evidence for Vaccine Synergy between Borrelia burgdorferi Decorin Binding Protein A and Outer Surface Protein A in the Mouse Model of Lyme Borreliosis

2000 ◽  
Vol 68 (11) ◽  
pp. 6457-6460 ◽  
Author(s):  
Mark S. Hanson ◽  
Nita K. Patel ◽  
David R. Cassatt ◽  
Nancy D. Ulbrandt
Keyword(s):  
Borrelia Burgdorferi ◽  
Outer Surface ◽  
Binding Protein ◽  
Protein A ◽  
Surface Protein ◽  
Outer Surface Protein A ◽  
Outer Surface Protein ◽  
Antigen Vaccine ◽  
Single Antigen

ABSTRACT Mice immunized with either the predominantly vector-stage lipoprotein outer surface protein A (OspA) or the in vivo-expressed lipoprotein decorin binding protein A (DbpA) are protected againstBorrelia burgdorferi challenge. DbpA-OspA combinations protected against 100-fold-higher challenge doses than did either single-antigen vaccine and conferred significant protection against heterologous B. burgdorferi, B. garinii, andB. afzelii isolates, suggesting that there is synergy between these two immunogens.

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