title: 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, n = 10) and patients with pneumococcal meningitis (n = 20) was analyzed. Spot differences were compared and identified between controls, nonsurvivors (n = 9), and survivors (n = 11).
  
  
  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.
authors.affiliation: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom. upali.goonetilleke@liverpool.ac.uk
authors.forename: Upali R
authors.initials: UR
authors.lastname: Goonetilleke
authors.forename: Matthew
authors.initials: M
authors.lastname: Scarborough
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Ward
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gordon
mesh_terms: D000328:Adult; D015415:Biomarkers; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008297:Male; D008586:Meningitis, Pneumococcal / Q000503:physiopathology*; D008875:Middle Aged; D020543:Proteome / Q000032:analysis*; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D020543:Proteome