The Role of Endotoxin Phosphoforms in Sepsis and Meningitis caused by Neisseria meningitidis. (#357)
Nisseria meningitidis is the largest cause of bacterial meningitis and fatal septic shock (1-3). Mortality rates are 50% if left untreated (4) making this disease one of the top 10 causes of worldwide death (3). N.meningitidis causes meningococcal meningitis and septic shock. In meningococcal meningitis the proliferation of bacteria is gradual compared to rapid proliferation that causes septic shock. The mechanism of action is unknown, however susceptibility depends on the immune complement system of individuals particularly in septic shock (3).
To determine binding of the endotoxin, the TLR-4/MD-2 protein complex is to be co-expressed in a Baculovirus expression system, and then purified on a Nickel affinity column. Lipid groups with varying phosphoforms will then to be soaked with protein crystals before sending crystals to the Australian Synchrotron in Melbourne for screening and collection of xray diffraction data.
- Rosenstein NE, Perkins BA, Stephens DS, Popovic T, Hughes JM. Meningococcal Disease. New England journal of medicine. 2001;344(18):1378.
- Stephens DS. Biology and pathogenesis of the evolutionarily successful, obligate human bacterium Neisseria meningitidis. Vaccine. 2009;27:B71-B7.
- Stephens DS, Greenwood B, Brandtzaeg P. Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. The Lancet. 2007;369(9580):2196-210.
- WHO. Meningococcal meningitis. [Fact Sheet] 2010 [cited 2011 11/06/2011].