Proteomic analysis of cerebrospinal fluid in pneumococcal meningitis reveals potential biomarkers associated with survival

Abstract

Background. Patients with pneumococcal meningitis often die or have severe neurological damage despite optimal antibiotic therapy. New or improved therapy is required. The delivery of new interventions will require an improved understanding of the disease pathogenesis. Our objective was to learn more about the pathophysiology of severe meningitis through the interpretation of differences in the proteomic profile of cerebrospinal fluid (CSF) from patients with meningitis. Methods. Two-dimensional polyacrylamide gel electrophoresis of CSF from normal subjects (controls, np ) and patients with pneumococcal meningitis ( ) was analyzed. Spot differences were compared 10 np20 and identified between controls, nonsurvivors (np9), and survivors (np11). Results. Protein concentration in CSF of patients with meningitis was 4-fold higher than in CSF of control subjects (7.0 mg/mL vs 0.23 mg/mL; P < .01). A mean of 2466 discrete protein spots was present in CSF of patients with meningitis. Thirty-four protein spots were differentially expressed in CSF of nonsurvivors, compared with survivors. None of these protein spots were observed in CSF of control subjects. Conclusions. Proteomic screening of CSF yields potential biomarkers capable of differentiating control subjects from nonsurvivors and survivors of meningitis. Proteins involved in the inflammatory process and central metabolism were represented in the differentially expressed protein repertoire. © 2010 by the Infectious Diseases Society of America.