Potential new therapies for meningococcal sepsis: Can we reduce tissue damage?
Why do cells and tissues in patients cease to function normally?
Dr David Dockrell, Dr Jay Laver, Prof Rob Read
- Start Date:
01 August 2009
University of Sheffield, Sheffield, UK
In meningococcal septicaemia and meningitis, patients deteriorate quickly and sometimes cannot be resuscitated despite treatment with fluids and drugs to support the circulation. The reason why meningococcal disease is so severe is unknown but the cells and tissues of patients cease to function in a normal way, despite the fact that, under the microscope, they look normal. One possible reason for this might be that vital chemicals have been lost from the cells because of the infection.
We have recently discovered that when the meningococcus infects cells, it uses a molecule called nitric oxide (NO). NO is important for normal functioning of the cells because it forms compounds called S-nitrosothiols or ‘SNO’, which in turn are required for proteins inside the cell to function in a normal way.
We found that infection with meningococcal bacteria causes cells to lose their SNO. Further work shows that this may have an impact on normal cell function. In this study we will confirm that loss of SNO in cells infected by the meningococcus disrupts three important and easily measurable normal cell functions.
Then, using mice, we will confirm that the tissues of the mouse show SNO loss, and that this has the effect that we observe in cells. We will then use a drug that is already available (GSNO) and which is capable of delivering SNO into tissues, and show whether it can reverse the damaging effects of SNO loss in mice.
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