Targets for new treatments.
Research archive
- University of Southampton, Southampton, UK
- Researchers:
Dr Myron Christodoulides, Professor John Heckels
- Project Number: 0206.0
- Category: Treatment
- Duration: 2003 -2007
- Start Date: 01 January 2003
- Type: Lay summary
- View scientific version
Prompt treatment of meningococcal disease with antibiotics, anti-inflammatory steroids (in meningitis) and intensive care management in hospital can significantly improve a patient's outlook, but we still need advanced treatments to reduce death and disability from this disease.
Meningococcal bacteria produce a substance called LPS (lipopolysaccharide), which is the main toxin that triggers inflammation and starts the devastating chain of events that leads to death and disability from meningitis and septicaemia. However, new therapies directed against LPS alone may not be the only way to advance treatment of the disease.
In this project, scientists are developing a novel approach to treatment: they aim to identify and investigate other substances that trigger inflammation as potential targets for future treatments. They will do this by finding out how different components of the bacteria interact with human cells involved in the disease and how the human cells respond. Finally, they will do tests to see whether these new targets they identify can be blocked in human cell cultures to assess their potential as new treatments.
Read our news release on this project:
Southampton scientists in meningitis research
Results from this study have been published in scientific journals as follows:
Al-Bader T, Christodoulides M, Heckels JE, Holloway J, Semper AE, Friedmann PS.
Activation of human dendritic cells is modulated by components of the outer membranes of Neisseria meningitidis.
Infect Immun 2003 Oct;71(10):5590-7.
http://iai.asm.org/cgi/reprint/71/10/5590.pdf
Al-Bader T, Jolley KA, Humphries HE, Holloway J, Heckels JE, Semper AE, Friedmann PS, Christodoulides M.
Activation of human dendritic cells by the PorA protein of Neisseria meningitidis.
Cell Microbiol 2004 Jul;6(7):651-62.
http://www.blackwell-synergy.com/doi/abs/10.1111/j.1462-5822.2004.00392.x
Humphries HE, Triantafilou M, Makepeace BL, Heckels JE, Triantafilou K, Christodoulides M.
Activation of human meningeal cells is modulated by lipopolysaccharide (LPS) and non-LPS components of Neisseria meningitidis and is independent of Toll-like receptor (TLR)4 and TLR2 signalling.
Cell Microbiol 2005 Mar;7(3):415-30.
http://www.blackwell-synergy.com/doi/abs/10.1111/j.1462-5822.2004.00471.x
Williams JN, Skipp PJ, Humphries HE, Christodoulides M, O'Connor CD, Heckels JE.
Proteomic Analysis of Outer Membranes and Vesicles from Wild-Type Serogroup B Neisseria meningitidis and a Lipopolysaccharide-Deficient Mutant
Infect Immun 2007 Mar;75(3):1364-72. Epub 2006 Dec 11.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed
Fowler MI, Yin KY, Humphries HE, Heckels JE, Christodoulides M.
Comparison of the inflammatory responses of human meningeal cells following challenge with Neisseria lactamica and with Neisseria meningitidis.
Infect Immun 2006 Nov;74(11):6467-78. Epub 2006 Sep 5.
http://iai.asm.org/cgi/content/abstract/74/11/6467