Meningococcal Disease and Future Drug Targets

L.      K. Gammelgaard; H.      Colding; S.      H. Hartzen; M.      Penkowa

doi:10.2174/187152711794488584

Abstract

Neisseria meningitidis (N. meningitidis) causes sepsis, epidemic meningitis, and sometimes also meningoencephalitis. Despite early antibiotic treatment, mortality and morbidity remain significant. We present recent studies on meningococcal disease with focus on the pathophysiology caused by bacterial virulence factors and the host immune responses. The bacterial outer membrane lipopolysaccharide and non-lipopolysaccharide components are related to meningococcal adhesion and invasion, while the host immune reactions propagate inflammation and neurodegeneration. Hence, bacterium-host interactions are key determinants of the clinical course and risk of fatal outcome. Accordingly, successful treatment of severe meningococcal disease requires not only antibiotics but also adjuvants targeting the released endotoxins and the host immune/inflammatory responses. This review highlights the most recent data and current knowledge on molecular mechanisms of meningococcal disease and explains how host immune responses ultimately may aggravate neuropathology and the clinical prognosis. Within this context, particular importance is paid to the endotoxic components that provide potential drug targets for novel neuroprotective adjuvants, which are needed in order to improve the clinical management of meningoencephalitis and patient prognosis.

Keywords: Inflammation, meningitis, infection, neuroprotection, medical treatment, N. meningitidis, nasopharynx, meningococcemia, meningococcal disease, L-glycero-D-mannoheptopyranoside, transferrin, lactoferrin, LPS, OMPs, CD66, ROS, brain parenchyma, Intraparenchymal neuropathology, encephalitis, hypertrophy, hyperplasia