Borrelia [Lyme Disease]

CRASP-1, or Complement Regulator-Acquiring Surface Protein 1, is a multifunctional protein of Lyme disease-causing B. burgdorferi that binds to several human extracellular matrix proteins and plasminogen, including factor H (resulting in inhibition of complement activation in mammals) and Human Bone Morphogenic Protein 2. These interactions may contribute to adhesion, bacterial colonization, and organ tropism and may allow dissemination of B. burgdorferi in the host. B. burgdorferi spirochetes express up to 5 complement regulator-acquiring surface proteins. Multiple copies of sequences analagous to CRASP-1 genes have been detected in Borrelia plasmids. Borrelia species contain a large number of plasmids, of linear and circular, some of which appear to repeat sequences or contain fragments of other genes. These regions may serve as potentially usable information for the survival of Borrelia in its multiple environments during its life cycle. In addition, the sequence for CRASP-1 contains a repeated sequence folded into a stable stem loop structure typical of RNA genes. Lyme disease proteins are ideal for researchers interested in immunology, neurology, rheumatology, coinfections, autoimmune, and neurodegenerative diseases.

Gene Name: CRASP1

CRASP-2 (Complement Regulator-Acquiring Surface Protein 2) of Borrelia burgdorferi binds FHL-1 and factor H binding protein in a distinct way. It may be predominantly expressed by serum-resistant Borrelia strains. Borrelia burgdorferi sensu lato has the ability to evade immune systems to persist in a variety of vertebrate hosts. This activity is dependent on a number of factors. Some Borrelia species bind host-derived fluid-phase immune regulators FHL-1 and factor H to their surface via complement regulator-acquiring surface proteins (CRASPs). Factor H and FHL-1 serve as cofactors for factor I, a serine protease that cleaves complement component 3b (C3b) directly on the cell surface and thereby confers resistance of spirochetes to complement-mediated lysis. It is possible that because of discontinuous binding regions in the factor H/FHL-1, long distance interaction may be involved in binding of both immune regulators. Putative coiled-coil structural elements may be important in the interaction of B. burgdorferi CRASP-1 with factor H. Lyme disease proteins are ideal for researchers interested in immunology, neurology, rheumatology, coinfections, autoimmune, and neurodegenerative diseases.

Gene Name: cspZ, BB_H06

DbpA, or Decorin Binding Protein A is from the spirochete Borrelia burgdorferi, which is carried by Ixodes ticks. DbpA from other microbial organisms such as E. coli (ATP-dependent RNA helicase DbpA) are significantly different. The spirochete migrates from the tick midgut during tick feeding to tick salivary glands and are thus transmitted to the mammal host. This transition may be facilitated by changes in expression of some B. burgdorferi genes. Spirochetal surface adhesions mediate attachment to decorin, a major component of the host extracellular matrix, enabling bacteria to colonize in mammalian tissues. It is believed that expression of the various proteins associated with the spirochete may be regulated by the changes in tick life cycle, changes in conditions during tick feeding (such as temperature, pH, and nutrients) and/or in coordination with the course of infection of the mammal host. Lyme disease proteins are ideal for researchers interested in immunology, neurology, rheumatology, coinfections, autoimmune, and neurodegenerative diseases.

Gene Name: dbpA, BB_A24

Decorin-binding protein B, or DbpB, binds to decorin, which may mediate the adherence of B. burgdorferi to collagen fibers in skin and other tissues. Spirochetal surface adhesions mediate attachment to decorin, a major component of the host extracellular matrix enabling bacteria to colonize in mammalian tissues. The spirochete migrates from the tick midgut during feeding to its salivary glands and are thus transmitted to the mammal host. This transition may be facilitated by changes in expression of some B. burgdorferi genes. It is believed that expression of the various proteins associated with the spirochete may be regulated by the changes in tick life cycle, changes in conditions during tick feeding (such as temperature, pH, and nutrients) and/or in coordination with the course of infection of the mammal host. Borrelia burgdorferi can colonize multiple tissues, and is capable of attachment to diverse cell types. The expression of decorin-binding protein (Dbp) A and/or DbpB, two B. burgdorferi surface proteins that bind GAGs, is sufficient to convert a high-passage nonadherent B. burgdorferi strain into one that efficiently binds 293 epithelial cells. Lyme disease proteins are ideal for researchers interested in immunology, neurology, rheumatology, coinfections, autoimmune, and neurodegenerative diseases.

Gene Name: dbpB, BB_A25

ErpD (ospE/F-Related Protein D), also known as Arp37, is from the spirochete Borrelia burgdorferi, which is carried by Ixodes ticks. Erp proteins from Borrelia burgdorferi are postulated to be lipoproteins, based on their predicted amino acid sequences. The spirochete migrates from the tick midgut during feeding to its salivary glands and are thus transmitted to the mammal host. This transition may be facilitated by changes in expression of some B. burgdorferi genes. It is believed that expression of the various proteins associated with the spirochete may be regulated by the changes in tick life cycle, changes in conditions during tick feeding (such as temperature, pH, and nutrients) and/or in coordination with the course of infection of the mammal host. Several studies have demonstrated that infected humans and animals produce antibodies directed against Erp proteins within the first 2-4 weeks of infection, indicative of Erp synthesis during the initial stages of vertebrate infection. It is postulated that surface-exposed Erp proteins could facilitate interactions with host tissues during the establishment of vertebrate infection. Lyme disease proteins are ideal for researchers interested in immunology, neurology, and rheumatology, coinfections, autoimmune, and neurodegenerative diseases.

Gene Name: BB_F01

ErpN (OspE/F-Related Protein N), is from the spirochete Borrelia burgdorferi, which is carried by Ixodes ticks. Erp proteins from Borrelia burgdorferi are postulated to be lipoproteins, based on their predicted amino acid sequences. The spirochete migrates from the tick midgut during feeding to its salivary glands and are thus transmitted to the mammal host. This transition may be facilitated by changes in expression of some B. burgdorferi genes. It is believed that expression of the various proteins associated with the spirochete may be regulated by the changes in tick life cycle, changes in conditions during tick feeding (such as temperature, pH, and nutrients) and/or in coordination with the course of infection of the mammal host. Several studies have demonstrated that infected humans and animals produce antibodies directed against Erp proteins within the first 2-4 weeks of infection, indicative of Erp synthesis during the initial stages of vertebrate infection. It is postulated that surface-exposed Erp proteins could facilitate interactions with host tissues during the establishment of vertebrate infection. Lyme disease proteins are ideal for researchers interested in immunology, neurology, and rheumatology, coinfections, autoimmune, and neurodegenerative diseases.

Gene Name: erpN, BB_L39

Flagellin is a protein found in the hollow cylinder forming the filament in bacterial flagellum. Its structure is helical, which is important for its function. Studies comparing a flagellate Borrelia to flagellated indicate that the flagella have a role in the invasion of human tissue. The N- and C-termini of flagellin form the inner core of the flagellar filament, and the central portion of the protein makes up the outer surface. While the terminus of the protein is quite similar between all bacterial flagellins, the central portion is variable. The flagellin genes are highly conserved among the different Borrelia species. Mammals often have acquired immune responses (T-cell and antibody responses) to flagellated bacterium. Some bacteria are able to switch between multiple flagellin genes in order to evade this response. Borrelia burgdorferi, the spirochete that is associated with Lyme Disease, may use this tactic when challenging mammals with infection. Borrelia have double-stranded linear plasmids in addition to supercoiled circular plasmids, in low copy number. This suggests that initiation of DNA replication and partitioning are carefully controlled during the cell division cycle. It is believed that expression of the various proteins associated with the spirochete may be regulated by the changes in tick life cycle, changes in conditions during tick feeding (such as temperature, pH, and nutrients) and/or in coordination with the course of infection of the mammal host, i.e., changes in environment as the spirochete migrates from the tick's midgut to its salivary glands to the mammal host. B. burgdorferi can attach to (and also differentially express antigens in) diverse tissues within the vertebrate host and the tick vector, suggesting that physiological factors other than pH and temperature may play roles in modulating B. burgdorferi gene expression. Lyme disease proteins are ideal for researchers interested in immunology, neurology, rheumatology, coinfections, autoimmune, and neurodegenerative diseases.

Gene Name: BBU94A_0149, fla

Outer-Surface Protein A (OspA), a lipoprotein from Borrelia burgdorferi encoded on its Plasmid lp54, is a major component of the spirochete's extracellular matrix. OspA probably serves as a lipid-anchor. The spirochetes migrate from the tick midgut during feeding to its salivary glands and are thus transmitted to the mammal host. This transition may be facilitated by changes in expression of some B. burgdorferi genes. Upon transmission of the spirochete from the Ixodes tick to mammalian host, the transcript level of OspA can change. It is believed that expression of the various proteins associated with the spirochete may be regulated by the changes in tick life cycle, changes in conditions during tick feeding (such as temperature, pH, and nutrients) and/or in coordination with the course of infection of the mammal host. B. burgdorferi can attach to (and also differentially express antigens in) diverse tissues within the vertebrate host and the tick vector, suggesting that physiological factors other than pH and temperature may play roles in modulating B. burgdorferi gene expression. Lyme disease proteins are ideal for researchers interested in immunology, neurology, rheumatology, coinfections, autoimmune, and neurodegenerative diseases.

Gene Name: ospA, BB_A15

OspB, is one of the major Outer Surface Proteins of the outer membrane of Borrelia burgdorferi, which is composed of various unique outer surface proteins (Osp) that have been characterized (OspA through OspF). The Osp proteins are lipoproteins anchored by N-terminally attached fatty acid molecules to the membrane. They are presumed to play a role in virulence, transmission, or survival in the tick. Two of the major surface Ag of Borrelia burgdorferi, the 31-kDa OspA and 34-kDa OspB proteins, show a high degree of sequence similarity, are encoded by a 49-kb plasmid and share a common promoter, and are coordinately transcribed. OspA, OspB, and OspD are expressed by B. burgdorferi residing in the gut of unfed ticks, suggesting that they promote the persistence of the spirochete in ticks between blood meals. OspB has a contributing role in the adherence of B. burgdorferi to the tick gut. The C terminus of OspB is important for eliciting a protective immune response to OspB. B. burgdorferi has the ability to vary its surface proteins in response to immune attack. Lyme disease proteins are ideal for researchers interested in immunology, neurology, rheumatology, coinfections, autoimmune, and neurodegenerative diseases.

Gene Name: ospB, locus BB_A16

Outer Surface Protein C, or OspC, is a 20.7 kDa immunogenic protein on the outer surface of the spirochete Borrelia burgdorferi. Its function is not known, but it is located with lipid-anchoring sites on the outer cell membrane. Lyme disease proteins are ideal for researchers interested in immunology, neurology, rheumatology, coinfections, autoimmune, and neurodegenerative diseases.

Gene Name: ospC, BB_B19

The p35 kDa protein of the spirochete Borrelia burgdorferi is being investigated for use as an early diagnostic marker of Lyme Disease. Borrelia may change its antigenic composition in its need for adaptation to stresses imposed by changes in conditions from cycling between its arthropod and mammalian hosts. This group of B. burgdorferi proteins may be induced in the tick midgut during the feeding event. The p35 protein elicits a protective immunity from wild type B. burgdorferi. It has been shown that p35 expression in B. burgdorferi is upregulated in the stationary growth phase, and that a temperature of 34°C but not 24°C influenced the expression. The expression of a majority of the proteins expressed in early Lyme disease is affected pH, being abundantly expressed at pH 7.0 (resembling the tick midgut pH of 6.8 during feeding) but only sparsely at pH 8.0 (a condition closer to that of the unfed tick midgut pH of 7.4). The encoding genes may be coregulated. The 35-kDa antigen has been shown to be a statistically significant marker in IgG immunoblots in a study of patients with early Lyme disease who presented with erythema migrans. Recombinant p35 protein may be useful as a diagnostic reagent, especially in combination with other antigens that have been deemed relevant in serodiagnosis of early Lyme disease. Lyme disease proteins are ideal for researchers interested in immunology, neurology, rheumatology, coinfections, autoimmune, and neurodegenerative diseases.

Gene Name: BB-H32, bba64

The p39 protein, or Basic membrane protein A, is one of the immunogenic cell membrane components of Borrelia burgdorferi, the spirochete carried by Ixodes ticks. The spirochete migrates from the tick midgut during feeding to its salivary glands and are thus transmitted to the mammal host. This transition may be facilitated by changes in expression of some B. burgdorferi genes. It is believed that expression of the various proteins associated with the spirochete may be regulated by the changes in tick life cycle, changes in conditions during tick feeding (such as temperature, pH, and nutrients) and/or in coordination with the course of infection of the mammal host. BmpA is expressed during the invasion of the spirochete and in the evolution of the arthritis of Lyme disease in mammals. It belongs to the BMP lipoprotein family. The major products of the B. burgdorferi basic membrane protein (bmp) A/B operon that are induced in murine and human joints possess inflammatory properties. Non-lipidated and lipidated versions of BmpA have been shown to induce the pro-inflammatory cytokine TNF-α and IL-1ß in human synovial cells. The induction of cytokine responses in synovial cells via activation of the NF-kappaB and p38 MAP kinase pathways could potentially contribute to the genesis of Lyme arthritis. The BmpA outer-surface protein is an important antigen for serodiagnosis of human infection. B. burgdorferi adheres to host extracellular matrix components, including laminin, but may not bind mammalian type I or type IV collagens or fibronectin. Lyme disease proteins are ideal for researchers interested in immunology, neurology, rheumatology, coinfections, autoimmune, and neurodegenerative diseases.

Gene Name: bmpA, BB_0383

Surface Lipoprotein p27 of Borrelia burgdorferi is a surface-exposed lipoprotein that has been shown (by Western blot and Northern blot) to be expressed in the European B. burgdorferi strain B29, but not in the American strain B31. Cell envelope proteins of bacterial pathogens play important roles in the host-parasite interactions that occur during infection, including cell adherence, cell invasion, and immune cell activation or evasion. p27 is a basic protein of 248 amino acids with a typical prokaryotic leader sequence of 17 amino acid residues at the N-terminus of the proposed translation product. The p27 gene is located on a linear plasmid of a size of approximately 55 kb. Borrelia spirochetes are unique among diderm bacteria in their abundance of surface-displayed lipoproteins, some of which play important roles in the pathogenesis of Lyme disease and relapsing fever. There is evidence that Borrelia lipoproteins are specifically targeted to the bacterial surface, but that they can be retained in the periplasm by sequence-specific signals. Lyme disease proteins are ideal for researchers interested in immunology, neurology, rheumatology, coinfections, autoimmune, and neurodegenerative diseases.

Gene Name: BB_A60

Variable Lipoprotein Surface-Exposed protein, or VlsE, is a lipoprotein on the surface of the Lyme Disease spirochete Borrelia burgdorferi, detectable during all its life stages. It can exist as many different isoforms. VlsE has variable regions (VRs) and invariable regions (IRs). Some IRs are anchored in the outer membrane of the bacteria and some are antigens exposed on the membrane surface. Replacement of the VR by Borrelia within days of being transferred to a mammalian host presents new surface antigens to the host immune system, and helps Borrelia avoid a strong reaction by host immune systems. The VlsE is apparently not modified as much in the tick or in the rodent vector, when compared to in the mammal host. Several putative envelope proteins of B. burgdorferi appear to be expressed only in the infected mammalian host. The VRs are antigenic, irregularly shaped loops on the bacterial surface which may help to hide both membrane-incorporated and surface portions of adjacent proteins from immune cells. These VR loops are coded by antigenic cassettes. The protein loops can therefore be switched in or out of the protein, or different type loops traded. In B. burgdorferi there seem to be at least fifteen different VlsE cassettes that can insert into any of the variable regions of VlsE, allowing it to appear as millions of different antigens. Similar, but smaller, systems also operate for OSP-A, OSP-B, OSP-C, and other proteins. Some current research involves determination of control of cassette activation. One IR region, C6, of the VlsE protein, consistently stimulates a strong immune response. Its presentation may be a decoy that misdirects the immune system from less protected sites by causing competition for binding antibodies. The bound antibodies are thus not available for binding important therapeutic proteins. This may help Borrelia to enter T-cells, leading to their destruction. Because IR6 is invariable and found in all life stages of B. burgdorferi, it has been used in an ELISA diagnostic test for early IgM of Lyme Disease. Lyme disease proteins are ideal for researchers interested in immunology, neurology, rheumatology, coinfections, autoimmune, and neurodegenerative diseases.

Gene Name: vlsE