June 7, 2010 Erik Georg Granquist's thesis examines infections caused by the bacterium Anaplasma phagocytophilum in lambs. This bacterium is the cause of the disease tick-borne fever in ruminants and granulocytic anaplasmosis in humans. The bacterium is transmitted by ticks and is the indirect cause of considerable animal welfare problems and financial losses in Norwegian sheep farming.
Granquist's findings have contributed to a better understanding of how the bacterium survives in the host animal over time. The results are an important step towards the development of a vaccination.
Granquist has researched variations in the bacterium's surface protein MSP2 (P44) -- the antigene that gives the largest immunogenic response and that consists of conserved and varied segments. Different proteins arise when gene segments combine, as the infection progresses. This is a strategy for evading the body's immune defence system. When the gene was cloned and sequenced as codes for MSP2 (P44) at different stages of an infection, large sequence variations in the surface protein were discovered.
By employing a number of different diagnostic methods, Granquist investigated how the immune system responds to antigene variation. He found that antibodies in infected lambs are targeted specifically at the different variants and areas of the bacterium's surface protein. He also observed that the serological reaction to variable and conserved surface proteins of the bacterium was short-lived and diminished over time.
In his thesis, Granquist studied how different variants of Anaplasma phagocytophilum carry out cyclic invasions of the blood. Lambs infected with one variant showed more frequent bacteraemia and had more circulating bacteria in their blood for a long time than lambs that were infected with another variant. Both variant-specific and individual differences in cyclic variation were revealed. This may be a clue as to why certain variants become more widespread in nature and can also explain why some variants of Anaplasma phagocytophilum lead to greater losses than other tick-infested pastures.
There has been a great deal of debate about whether endothelial cells may be important components in the development of infections and prolonged infections due to Anaplasma phagocytophilum. For this reason, Granquist studied skin biopsies from tick bites on lambs which had been naturally infected with Anaplasma phagocytophilum. His research revealed that the bacterium is seldom associated with endothelial cells, but can be found in other parts of the blood vessel wall and in infiltrates in infected cells around the tick bite. By means of substances in its spit, the tick can attract infected cells which are important for the bacterium's life cycle. These discoveries indicate that the skin can act as an important storage depot for bacteria.
Doctor of Veterinary Medicine Erik Georg Granquist presented his doctoral thesis on 2nd June 2010 for the title of Philosophiae Doctor (PhD) at The Norwegian School of Veterinary Science. His thesis is entitled: "Infection strategies and immune evasion of Anaplasma phagocytophilum in lambs"
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