G18secL03Tpc4: Difference between revisions

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=== Major Hypothesized Functions ===

*Adaptation and survival in different host environments

Borrelia burgdorferi expresses OspA but not OspC when residing in the midgut of unfed ticks. However, when the tick starts feeding on mammals, OspC synthesis is induced and OspA is repressed.The switch is in part due to the change in temperature; OspC is induced at 32–37°C, but not at 24°C, and this upregulation is at the transcriptional and translational levels. Evidence suggests co-regulation of these two genes at the mRNA level. Clearly, to survive in both hosts, spirochetes have evolved mechanisms for sensing the different host environments and responding accordingly.<ref>D. Kumaran1, S. Eswaramoorthy1, B.J. Luft2, S. Koide3, J.J. Dunn1, C.L. Lawson1,4 and S. Swaminathan1. Crystal structure of outer surface protein C (OspC) from the Lyme disease spirochete, Borrelia burgdorferi.The EMBO Journal (2001) 20, 971 - 978 [http://dx.doi.org/DOI:10.1093/emboj/20.5.971]</ref>

''Borrelia burgdorferi'' expresses OspA but not OspC when residing in the midgut of unfed ticks. However, when the tick starts feeding on mammals, OspC synthesis is induced and OspA is repressed.The switch is in part due to the change in temperature; OspC is induced at 32–37°C, but not at 24°C, and this upregulation is at the transcriptional and translational levels. Evidence suggests co-regulation of these two genes at the mRNA level. Clearly, to survive in both hosts, spirochetes have evolved mechanisms for sensing the different host environments and responding accordingly.<ref>D. Kumaran1, S. Eswaramoorthy1, B.J. Luft2, S. Koide3, J.J. Dunn1, C.L. Lawson1,4 and S. Swaminathan1. Crystal structure of outer surface protein C (OspC) from the Lyme disease spirochete, Borrelia burgdorferi.The EMBO Journal (2001) 20, 971 - 978 [http://dx.doi.org/DOI:10.1093/emboj/20.5.971]</ref>

*Binding and attachment to host's tissues

OspC may possibly be a binding protein contributing to a fundamental biological process and determining virulence of the bacteria. Several studies have shown that ''B.burgdorferi'' has a predilection for collagenous tissue and can interact with fibronectin and cellular collagens. The spirochetes can bind to a number of different cell types, including fibroblasts. ''Borrelia burgdorferi'' can bind to a novel circulating fibroblast-like cell called the peripheral blood fibrocyte, which expresses collagen types I and III as well as fibronectin, in a process that does not require OspA or OspB.<ref>PMID:10072447</ref>

OspC may possibly be a binding protein contributing to a fundamental biological process and determining virulence of the bacteria. Several studies have shown that ''B.burgdorferi'' has a predilection for [http://en.wikipedia.org/wiki/Collagen collagenous] tissue and can interact with [http://en.wikipedia.org/wiki/Fibronectin fibronectin] and cellular collagens. The spirochetes can bind to a number of different cell types, including [http://en.wikipedia.org/wiki/Fibroblast fibroblasts]. ''Borrelia burgdorferi'' can bind to a novel circulating fibroblast-like cell called the peripheral blood fibrocyte, which expresses collagen types I and III as well as fibronectin, in a process that does not require OspA or OspB.<ref>PMID:10072447</ref>

==== Putative Binding Site ====

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==== Main Advantages of Developing OspC-based Vaccine ====

Unlike OspC, the OspA protein is only present in the Borrelia burgdorferi while they are in the midgut of the cold blooded tick, and not in the host. Once the tick begins to feed on its warm blooded mammalian host, the Borrelia burgdorferi migrate from the midgut of the tick to the salivary glands and OspC is produced in the host's bloodstream. <ref>D. Greenburg, M.S. Rowe. Brookhaven Scientists Determine Key Lime Disease Protein Structure.Brookhaven National Laboratory (2001)[http://www.bnl.gov/bnlweb/pubaf/pr/2001/bnlpr022801.htm]</ref> Because of this, when a host is vaccinated with the OspA vaccine, antibodies to the OspA protein can only kill the bacteria inside of the tick if it ingests the antibodies during feeding. <ref>D. Greenburg, M.S. Rowe. Brookhaven Scientists Determine Key Lime Disease Protein Structure.Brookhaven National Laboratory (2001)[http://www.bnl.gov/bnlweb/pubaf/pr/2001/bnlpr022801.htm]</ref> If the bacteria enter the host, it can differentiate into several forms for which the vaccine cannot protect against. In contrast, an OspC based vaccine would allow the host to make antibodies to kill the Borrelia burgdorferi after they enter the host's body. <ref>D. Greenburg, M.S. Rowe. Brookhaven Scientists Determine Key Lime Disease Protein Structure.Brookhaven National Laboratory (2001)[http://www.bnl.gov/bnlweb/pubaf/pr/2001/bnlpr022801.htm]</ref>

Unlike OspC, the OspA protein is only present in the ''Borrelia burgdorferi'' while they are in the midgut of the cold blooded tick, and not in the host. Once the tick begins to feed on its warm blooded mammalian host, the ''Borrelia burgdorferi'' migrate from the midgut of the tick to the salivary glands and OspC is produced in the host's bloodstream. <ref>D. Greenburg, M.S. Rowe. Brookhaven Scientists Determine Key Lime Disease Protein Structure.Brookhaven National Laboratory (2001)[http://www.bnl.gov/bnlweb/pubaf/pr/2001/bnlpr022801.htm]</ref> Because of this, when a host is vaccinated with the OspA vaccine, antibodies to the OspA protein can only kill the bacteria inside of the tick if it ingests the antibodies during feeding. <ref>D. Greenburg, M.S. Rowe. Brookhaven Scientists Determine Key Lime Disease Protein Structure.Brookhaven National Laboratory (2001)[http://www.bnl.gov/bnlweb/pubaf/pr/2001/bnlpr022801.htm]</ref> If the bacteria enter the host, it can differentiate into several forms for which the vaccine cannot protect against. In contrast, an OspC based vaccine would allow the host to make antibodies to kill the Borrelia burgdorferi after they enter the host's body. <ref>D. Greenburg, M.S. Rowe. Brookhaven Scientists Determine Key Lime Disease Protein Structure.Brookhaven National Laboratory (2001)[http://www.bnl.gov/bnlweb/pubaf/pr/2001/bnlpr022801.htm]</ref>

==== Main Problems with Application of OspC-based Vaccine ====

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@@ Line 15: / Line 15: @@
 === Major Hypothesized Functions ===
 *Adaptation and survival in different host environments
-Borrelia burgdorferi expresses OspA but not OspC when residing in the midgut of unfed ticks. However, when the tick starts feeding on mammals, OspC synthesis is induced and OspA is repressed.The switch is in part due to the change in temperature; OspC is induced at 32–37°C, but not at 24°C, and this upregulation is at the transcriptional and translational levels. Evidence suggests co-regulation of these two genes at the mRNA level. Clearly, to survive in both hosts, spirochetes have evolved mechanisms for sensing the different host environments and responding accordingly.<ref>D. Kumaran1, S. Eswaramoorthy1, B.J. Luft2, S. Koide3, J.J. Dunn1, C.L. Lawson1,4 and S. Swaminathan1. Crystal structure of outer surface protein C (OspC) from the Lyme disease spirochete, Borrelia burgdorferi.The EMBO Journal (2001) 20, 971 - 978 [http://dx.doi.org/DOI:10.1093/emboj/20.5.971]</ref>
+''Borrelia burgdorferi'' expresses OspA but not OspC when residing in the midgut of unfed ticks. However, when the tick starts feeding on mammals, OspC synthesis is induced and OspA is repressed.The switch is in part due to the change in temperature; OspC is induced at 32–37°C, but not at 24°C, and this upregulation is at the transcriptional and translational levels. Evidence suggests co-regulation of these two genes at the mRNA level. Clearly, to survive in both hosts, spirochetes have evolved mechanisms for sensing the different host environments and responding accordingly.<ref>D. Kumaran1, S. Eswaramoorthy1, B.J. Luft2, S. Koide3, J.J. Dunn1, C.L. Lawson1,4 and S. Swaminathan1. Crystal structure of outer surface protein C (OspC) from the Lyme disease spirochete, Borrelia burgdorferi.The EMBO Journal (2001) 20, 971 - 978 [http://dx.doi.org/DOI:10.1093/emboj/20.5.971]</ref>
 *Binding and attachment to host's tissues
-OspC may possibly be a binding protein contributing to a fundamental biological process and determining virulence of the bacteria. Several studies have shown that ''B.burgdorferi'' has a predilection for collagenous tissue and can interact with fibronectin and cellular collagens. The spirochetes can bind to a number of different cell types, including fibroblasts. ''Borrelia burgdorferi'' can bind to a novel circulating fibroblast-like cell called the peripheral blood fibrocyte, which expresses collagen types I and III as well as fibronectin, in a process that does not require OspA or OspB.<ref>PMID:10072447</ref>
+OspC may possibly be a binding protein contributing to a fundamental biological process and determining virulence of the bacteria. Several studies have shown that ''B.burgdorferi'' has a predilection for [http://en.wikipedia.org/wiki/Collagen collagenous] tissue and can interact with [http://en.wikipedia.org/wiki/Fibronectin fibronectin] and cellular collagens. The spirochetes can bind to a number of different cell types, including [http://en.wikipedia.org/wiki/Fibroblast fibroblasts]. ''Borrelia burgdorferi'' can bind to a novel circulating fibroblast-like cell called the peripheral blood fibrocyte, which expresses collagen types I and III as well as fibronectin, in a process that does not require OspA or OspB.<ref>PMID:10072447</ref>
 ==== Putative Binding Site ====
 <Structure load='1ggq' size='400' frame='true' align='right' caption=' ' scene='Insert optional scene name here' />
@@ Line 31: / Line 31: @@
 ==== Main Advantages of Developing OspC-based Vaccine ====
-Unlike OspC, the OspA protein is only present in the Borrelia burgdorferi while they are in the midgut of the cold blooded tick, and not in the host. Once the tick begins to feed on its warm blooded mammalian host, the Borrelia burgdorferi migrate from the midgut of the tick to the salivary glands and OspC is produced in the host's bloodstream. <ref>D. Greenburg, M.S. Rowe. Brookhaven Scientists Determine Key Lime Disease Protein Structure.Brookhaven National Laboratory (2001)[http://www.bnl.gov/bnlweb/pubaf/pr/2001/bnlpr022801.htm]</ref> Because of this, when a host is vaccinated with the OspA vaccine, antibodies to the OspA protein can only kill the bacteria inside of the tick if it ingests the antibodies during feeding. <ref>D. Greenburg, M.S. Rowe. Brookhaven Scientists Determine Key Lime Disease Protein Structure.Brookhaven National Laboratory (2001)[http://www.bnl.gov/bnlweb/pubaf/pr/2001/bnlpr022801.htm]</ref> If the bacteria enter the host, it can differentiate into several forms for which the vaccine cannot protect against. In contrast, an OspC based vaccine would allow the host to make antibodies to kill the Borrelia burgdorferi after they enter the host's body. <ref>D. Greenburg, M.S. Rowe. Brookhaven Scientists Determine Key Lime Disease Protein Structure.Brookhaven National Laboratory (2001)[http://www.bnl.gov/bnlweb/pubaf/pr/2001/bnlpr022801.htm]</ref>
+Unlike OspC, the OspA protein is only present in the ''Borrelia burgdorferi'' while they are in the midgut of the cold blooded tick, and not in the host. Once the tick begins to feed on its warm blooded mammalian host, the ''Borrelia burgdorferi'' migrate from the midgut of the tick to the salivary glands and OspC is produced in the host's bloodstream. <ref>D. Greenburg, M.S. Rowe. Brookhaven Scientists Determine Key Lime Disease Protein Structure.Brookhaven National Laboratory (2001)[http://www.bnl.gov/bnlweb/pubaf/pr/2001/bnlpr022801.htm]</ref> Because of this, when a host is vaccinated with the OspA vaccine, antibodies to the OspA protein can only kill the bacteria inside of the tick if it ingests the antibodies during feeding. <ref>D. Greenburg, M.S. Rowe. Brookhaven Scientists Determine Key Lime Disease Protein Structure.Brookhaven National Laboratory (2001)[http://www.bnl.gov/bnlweb/pubaf/pr/2001/bnlpr022801.htm]</ref> If the bacteria enter the host, it can differentiate into several forms for which the vaccine cannot protect against. In contrast, an OspC based vaccine would allow the host to make antibodies to kill the Borrelia burgdorferi after they enter the host's body. <ref>D. Greenburg, M.S. Rowe. Brookhaven Scientists Determine Key Lime Disease Protein Structure.Brookhaven National Laboratory (2001)[http://www.bnl.gov/bnlweb/pubaf/pr/2001/bnlpr022801.htm]</ref>
 ==== Main Problems with Application of OspC-based Vaccine ====