Pathogenic significance of meningococcal IgA1 protease
Dr Jon Sayers, Dr Robert Read, Dr Steven Dower
- Start Date:
01 January 2000
University of Sheffield, Sheffield, UK
Even when treated in specialised hospital units, invasive meningococcal disease has a 5-20% mortality with a similar percentage suffering lasting sequelae. Neisseria meningitidis produces a protease able to degrade human IgA1, a key mediator of mucosal defense. Meyer et al have shown that the closely related Neisseria gonorrhoeae IgA protease is a potent dose-dependent inducer of pro-inflammatory cytokines (TNFa, IL-6) and So et al have shown it facilitates trafficking of bacteria through epithelial cells. Furthermore, pilot studies conducted in this laboratory provide strong evidence that blood and CSF isolates of Neisseria meningitidis from patients with meningococcal disease produce significantly higher (P < 0.0001) levels of IgA1 protease than throat isolates of N. meningitidis from asymptomatic carriers. It seems reasonable to assume that IgA protease contributes to pathology. We wish to investigate the roles played by meningococcal IgA protease and the mechanisms responsible for increased IgA protease activity. These studies may confirm IgA protease as a target for therapeutic intervention.
Read our news release about this project:
Scientists discover how meningitis defeats our immune system
Results from this study have been published in scientific journals as follows:
Parsons HK, Vitovski S, Sayers JR.
Immunoglobulin A1 proteases: a structure-function update.
Biochem Soc Trans 2004 Dec;32(Pt 6):1130-2.
Vitovski S, Sayers J.
Relaxed cleavage specificity of an IgA1 protease from Neisseria meningitidis.
Infect Immun 2007 Mar 12; [Epub ahead of print].