Investigating Bacterial Penetration of the Blood-Brain Barrier for the Pathogenesis, Prevention, and Therapy of Bacterial Meningitis

Abstract

The most distressing aspect of bacterial meningitis is limited improvement in the mortality and morbidity despite attributable advances in antimicrobial chemotherapy and supportive care. A major contributing factor to such mortality and morbidity is our incomplete understanding of the pathogenesis of this disease. Microbial penetration of the blood-brain barrier, a prerequisite for the development of bacterial meningitis, exploits specific host and bacterial factors as well as host cell signaling molecules. Determination and characterization of such host and bacterial factors have been instrumental for developing our current knowledge on the pathogenesis of bacterial meningitis. In addition, counteracting such host and microbial factors has been shown to be efficacious in the prevention of bacterial meningitis. Antimicrobial therapy alone has limited efficacy in improving the outcome of bacterial meningitis. Recent studies suggest that counteracting targets contributing to bacterial penetration of the blood-brain barrier are a beneficial therapeutic adjunct to antimicrobial therapy in improving the outcome of bacterial meningitis. Taken together, these findings indicate that the elucidation of host and bacterial factors contributing to microbial penetration of the blood-brain barrier provides a novel strategy for investigating the pathogenesis, prevention, and therapy of bacterial meningitis.

Keywords: bacterial meningitis; blood−brain barrier; pathogenesis; prevention; therapy.