Abstract
The immunological response in bacterial meningitis (BM) causes the formation of reactive oxygen and nitrogen species (ROS, RNS) and activates myeloperoxidase (MPO), an inflammatory enzyme. Thus, structural oxidative and nitrosative damage to proteins and DNA occurs. We aimed to asses these events in the cerebrospinal fluid (CSF) of pediatric BM patients. Phenylalanine (Phe), para-tyrosine (p-Tyr), nucleoside 2′-deoxiguanosine (2dG), and biomarkers of ROS/RNS-induced protein and DNA oxidation: ortho-tyrosine (o-Tyr), 3-chlorotyrosine (3Cl-Tyr), 3-nitrotyrosine (3NO₂-Tyr) and 8-oxo-2′-deoxyguanosine (8OHdG), concentrations were measured by liquid chromatography coupled to tandem mass spectrometry in the initial CSF of 79 children with BM and 10 without BM. All biomarkers, normalized with their corresponding precursors, showed higher median concentrations (p < 0.0001) in BM compared with controls, except 8OHdG/2dG. The ratios o-Tyr/Phe, 3Cl-Tyr/p-Tyr and 3NO₂-Tyr/p-Tyr were 570, 20 and 4.5 times as high, respectively. A significantly higher 3Cl-Tyr/p-Tyr ratio was found in BM caused by Streptococcus pneumoniae, than by Haemophilus influenzae type b, or Neisseria meningitidis (p = 0.002 for both). In conclusion, biomarkers indicating oxidative damage to proteins distinguished BM patients from non-BM, most clearly the o-Tyr/Phe ratio. The high 3Cl-Tyr/p-Tyr ratio in pneumococcal meningitis suggests robust inflammation because 3Cl-Tyr is a marker of MPO activation and, indirectly, of inflammation.
Highlights
Despite improved vaccination programs and antibiotics, bacterial meningitis (BM) remains the tenth leading cause of global under-5 deaths [1]
A significantly higher 3Cl-Tyr/p-Tyr ratio was found in BM caused by Streptococcus pneumoniae, than by Haemophilus influenzae type b, or Neisseria meningitidis (p = 0.002 for both)
A negative correlation existed between the concentrations of Phe (Rho −0.26, p = 0.02449, p-Tyr (Rho −0.413, p = 0.0003), 3Cl-Tyr (Rho −0.261, p = 0.022) and cerebrospinal fluid (CSF) glucose
Summary
Despite improved vaccination programs and antibiotics, bacterial meningitis (BM) remains the tenth leading cause of global under-5 deaths [1]. It can lead to serious sequelae such as cognitive deficit, hearing loss, motor deficit, seizures, visual impairment, or hydrocephalus [2]. Antioxidants 2019, 8, 441 space (SAS) and the host’s strong inflammatory reaction [3,4]. When recognizing bacterial components in the SAS, Toll-like and other receptors of the innate immune system cause activation of nuclear factor kappa B (NF-κB). This in turn regulates the expression of pro-inflammatory cytokines and chemokines [5].
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