G14secL04Tpc3: Difference between revisions

Lyme disease is caused by the bacterial spirochete ''Borrelia burgdorferi sensu lato''. It is an inflammatory disorder that usually begins with skin lesions known as erythema chronicum migrands (ECM)<ref name ="sbu">http://www.jstor.org/stable/1689391</ref>. Months later the skin lesion can be followed by cardiac or neurological symptoms, migratory polyarthritis, oligoarticular arthritis, and chronic arthritis in the knees<ref name="sbu" />. The disease was first recognized as a new form of inflammatory arthritis in Lyme, Conneticuit in 1975. Since then, the disease has been reported from many other parts of the United States<ref name="sbu" />.

Colonization and survival of ''Borrelia burgdorferi'' within ticks and mammals is facilitated, in part, by [http://en.wikipedia.org/wiki/Lipoprotein lipoproteins]. OspB and OspA are two of the major lipoproteins present on the outer surface of the spirochete Borrelia Burgdoferi. Studies have shown that OspB is critical for the adherence of the spirochete to the gut wall of its tick vector<ref name ="critical">http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.0030033</ref>. The free OspB structure consists of a barrel domain which might be the portion that interacts with a protein or a linear saccharide in the tick-gut, promoting the attachment of spirochete on the tick gut<ref name="1rjl_pdb">http://www.jbc.org/content/280/17/17363.full</ref>.  It’s speculated that destroying these lipoproteins will cause bacterial death of spirochetes.  Some antibody Fab fragments such as H6831 and CB2 have been shown to cause bacterial lysis of spirochetes by binding to these lipoproteins in the absence of phagocytes and without [http://en.wikipedia.org/wiki/Complement_system complement], which is normally part of the immune response to bacteria<ref name ="1rjl_pdb" />. However, it remains unclear how binding of H6831 or CB2 can lead directly to lysis of the bacterium.

It was observed that after entry into the ticks, B. burgdorferi replicates and persists within the gut, then during a subsequent blood meal, migrates through the vector and is transmitted to a new host.<ref name="transmit">http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Search&doptcmdl=Citation&defaultField=Title%20Word&term=De%20Silva%5Bauthor%5D%20AND%20Growth%20and%20migration%20of%20Borrelia%20burgdorferi%20in%20Ixodes%20ticks%20during%20blood%20feeding</ref>. Other studies show that the expression of B. burgdorferi OspA and OspB is immediately turned on when the spirochetes enter and reside within the arthropod vector<ref name="transmit" />. However, during transmission from the arthropod vector to a vertebrate host, expression of B. burgdorferi are downregulated. Since OspA and OspB  are critical for the adherence of  the spirochete to the mid-gut of the tick, if this protein is down- regulated or expressed less, then it will attach less to the mid-gut of the tick and as a result be more likely to be excreted in some way into the host on which the tick is feeding.