BBE31 from the Lyme disease agent Borrelia burgdorferi, known to play an important role in successful colonization of the mammalian host, shows the ability to bind glutathione
Abstract Lyme disease is a tick-borne infection caused by Borrelia burgdorferi sensu lato complex spirochetes. The spirochete is located in the gut of the tick; as the infected tick starts the blood meal, the spirochete must travel through the hemolymph to the salivary glands, where it can spread to and infect the new host organism. In this study, we determined the crystal structures of the key outer surface protein BBE31 from B. burgdorferi and its orthologous protein BSE31 (BSPA14S_RS05060 gene product) from B. spielmanii. BBE31 is known to be important for the transfer of B. burgdorferi from the gut to the hemolymph in the tick after a tick bite. While BBE31 exerts its function by intera…
Crystal structure of the infectious phenotype-associated outer surface protein BBA66 from the Lyme disease agent Borrelia burgdorferi
Borrelia burgdorferi, the causative agent of Lyme disease is transmitted to the mammalian host organisms by infected Ixodes ticks. Transfer of the spirochaetal bacteria from Ixodes ticks to the warm-blooded mammalian organism provides a challenge for the bacteria to adapt and survive in the different environmental conditions. B. burgdorferi has managed to differentially express genes in response to the encountered changes such as temperature and pH variance or metabolic rate to survive in both environments. In recent years, much interest has been turned on genes that are upregulated during the borrelial transfer to mammalian organisms as this could reveal the proteins important in the patho…
Structural analysis of the infectious phenotype associated outer surface lipoproteins from Borrelia burgdorferi paralogous gene family PFam54
Laima slimība ir ērču pārnēsāta infekcijas slimība, kuras izraisītājs ir spiroheta Borrelia burgdorferi. Inficētu Ixodes ērču barošanās laikā baktērija var nonākt zīdītāja organismā. Ērcei uzsākot asins sūkšanas procesu, B. burgdorferi spēj izmainīt vairāku gēnu ekspresijas līmeni kā atbildes reakciju uz temperatūras, šūnu blīvuma, pH un barības vielu pieejamības izmaiņām. Daudzi no B. burgdorferi gēniem, kuru ekspresijā tiek novērotas izteiktas izmaiņas, kodē dažādus ārējās virsmas proteīnus, savukārt šie ārējās virmas proteīni tiek saistīti ar Laima slimības patoģenēzi. Tieši ārējās virsmas proteīni var potenciāli nodrošināt baktērijas pārnesi no ērces uz zīdītāja organismu, kā arī pielāg…
Structural and Functional Analysis of BBA03, Borrelia burgdorferi Competitive Advantage Promoting Outer Surface Lipoprotein
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 …
Crystal structure of the N-terminal domain of the major virulence factor BB0323 from the Lyme disease agent Borrelia burgdorferi.
Lyme disease is an infection caused by the spirochete Borrelia burgdorferi after it is transmitted to a mammalian organism during a tick blood meal. B. burgdorferi encodes at least 140 lipoproteins located on the outer or inner membrane, thus facing the surroundings or the periplasmic space, respectively. However, most of the predicted lipoproteins are of unknown function, and only a few proteins are known to be essential for the persistence and virulence of the pathogen. One such protein is the periplasmic BB0323, which is indispensable for B. burgdorferi to cause Lyme disease and the function of which is associated with cell fission and outer membrane integrity. After expression and trans…
Structure of an outer surface lipoprotein BBA64 from the Lyme disease agent Borrelia burgdorferi which is critical to ensure infection after a tick bite.
Lyme disease is a tick-borne infection caused by the transmission of Borrelia burgdorferi from infected Ixodes ticks to a mammalian host during the blood meal. Previous studies have shown that the expression of B. burgdorferi surface-localized lipoproteins, which include BBA64, is up-regulated during the process of tick feeding. Although the exact function of BBA64 is not known, this lipoprotein is critical for the transmission of the spirochete from the tick salivary glands to the mammalian organism after a tick bite. Since the mechanism of development of the disease and the functions of the surface lipoproteins associated with borreliosis are still poorly understood, the crystal structur…
Structural analysis of Borrelia burgdorferi periplasmic lipoprotein BB0365 involved in Lyme disease infection.
The periplasmic lipoprotein BB0365 of the Lyme disease agent Borrelia burgdorferi is expressed throughout mammalian infection and is essential for all phases of Lyme disease infection; its function, however, remains unknown. In the current study, our structural analysis of BB0365 revealed the same structural fold as that found in the NqrC and RnfG subunits of the NADH:quinone and ferredoxin:NAD+ sodium-translocating oxidoreductase complexes, which points to a potential role for BB0365 as a component of the sodium pump. Additionally, BB0365 coordinated Zn2+ by the His51, His55, His140 residues, and the Zn2+ -binding site indicates that BB0365 could act as a potential metalloenzyme; therefore…
Structural characterization of the Borrelia burgdorferi outer surface protein BBA73 implicates dimerization as a functional mechanism.
Borrelia burgdorferi, which is the causative agent of Lyme disease, is transmitted from infected Ixodes ticks to a mammalian host following a tick bite. Upon changing the host organism from an Ixodes tick to a warm-blooded mammal, the spirochete must adapt to very different conditions, which is achieved by altering the expression of several genes in response to a changing environment. Recently, considerable attention has been devoted to several outer surface proteins, including BBA73, that undergo dramatic upregulation during the transmission of B. burgdorferi from infected Ixodes ticks to mammals and that are thought to be important for the establishment and maintenance of the infection. T…
Solution NMR structure of Borrelia burgdorferi outer surface lipoprotein BBP28, a member of the mlp protein family.
Lyme disease is the most widespread vector‐transmitted disease in North America and Europe, caused by infection with Borrelia burgdorferi sensu lato complex spirochetes. We report the solution NMR structure of the B. burgdorferi outer surface lipoprotein BBP28, a member of the multicopy lipoprotein (mlp) family. The structure comprises a tether peptide, five α‐helices and an extended C‐terminal loop. The fold is similar to that of Borrelia tunicate outer surface protein BTA121, which is known to bind lipids. These results contribute to the understanding of Lyme disease pathogenesis by revealing the molecular structure of a protein from the widely found mlp family. This article is protected …
Structural characterization of CspZ, a complement regulator factor H and FHL-1 binding protein fromBorrelia burgdorferi
Borrelia burgdorferi is the causative agent of Lyme disease and is found in two different types of hosts in nature - Ixodes ticks and various mammalian organisms. To initiate disease and survive in mammalian host organisms, B. burgdorferi must be able to transfer to a new host, proliferate, attach to different tissue and resist the immune response. To resist the host's immune response, B. burgdorferi produces at least five different outer surface proteins that can bind complement regulator factor H (CFH) and/or factor H-like protein 1 (CFHL-1). The crystal structures of two uniquely folded complement binding proteins, which belong to two distinct gene families and are not found in other bac…
Borrelia burgdorferi infekciozā fenotipa saistīto ārējo virsmas proteīnu, kas pieder paralogajai gēnu saimei Pfam54, strukturālā analīze
Laima slimība ir ērču pārnēsāta infekcijas slimība, kuras izraisītājs ir spiroheta Borrelia burgdorferi. Inficētu Ixodes ērču barošanās laikā baktērija var nonākt zīdītāja organismā. Ērcei uzsākot asins sūkšanas procesu, B. burgdorferi spēj izmainīt vairāku gēnu ekspresijas līmeni kā atbildes reakciju uz temperatūras, šūnu blīvuma, pH un barības vielu pieejamības izmaiņām. Daudzi no B. burgdorferi gēniem, kuru ekspresijā tiek novērotas izteiktas izmaiņas, kodē dažādus ārējās virsmas proteīnus, savukārt šie ārējās virmas proteīni tiek saistīti ar Laima slimības patoģenēzi. Tieši ārējās virsmas proteīni var potenciāli nodrošināt baktērijas pārnesi no ērces uz zīdītāja organismu, kā arī pielāg…
Fibronectin-binding nanoparticles for intracellular targeting addressed by B. burgdorferi BBK32 protein fragments.
Virus-like particles (VLPs) are created by the self-assembly of multiple copies of envelope and/or capsid proteins from many viruses, mimicking the conformation of a native virus. Such noninfectious nanostructures are mainly used as antigen-presenting platforms, especially in vaccine research; however, some of them recently were used as scaffolds in biotechnology to produce targeted nanoparticles for intracellular delivery. This study demonstrates the creation of fusion VLPs using hepatitis B core protein-based system maintaining a fibronectin-binding property from B. burgdorferi BBK32 protein, including the evidence of particles’ transmission to BHK-21 target cells via caveolae/rafts endoc…