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Quantitative Proteomics of Cerebrospinal Fluid in Paediatric Pneumococcal Meningitis
Guadalupe Gómez-Baena1, Richard J Bennett1, Carmen Martínez-Rodríguez2
1Centre for Proteome Research, Institute of Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, United Kingdom.
Insights
This study identified key protein changes in cerebrospinal fluid of children with Streptococcus pneumoniae meningitis, revealing immune response and exosome signaling as crucial factors for better treatment strategies.
Area of Science:
- Neuroscience
- Infectious Diseases
- Proteomics
Background:
- Streptococcus pneumoniae causes severe global health issues like meningitis, pneumonia, and septicaemia.
- Pneumococcal meningitis remains life-threatening, with survivors often facing long-term sequelae.
- Understanding central nervous system processes is vital for improved pneumococcal meningitis management.
Purpose of the Study:
- To identify protein alterations in cerebrospinal fluid (CSF) of children with Streptococcus pneumoniae meningitis.
- To compare protein profiles between infected children and controls with meningitis symptoms but negative diagnoses.
- To uncover potential biomarkers and therapeutic targets for pneumococcal meningitis.
Main Methods:
- Quantitative proteomics using mass spectrometry (label-free) was employed on CSF samples from two independent patient cohorts.
- Differential protein expression analysis was conducted to identify proteins significantly altered in pneumococcal meningitis cases.
- Proteomics findings were validated in a third cohort using automated quantitative western blotting.
Main Results:
- Over 200 human proteins were differentially expressed in each cohort, with 65% overlap between them.
- Proteins associated with immune response and exosome signaling pathways were significantly enriched in infected CSF samples.
- Western blotting confirmed the proteomics data, showing excellent agreement.
Conclusions:
- Proteomic analysis of CSF reveals significant changes in protein expression during Streptococcus pneumoniae meningitis.
- Immune response and exosome signaling proteins are key players in the pathogenesis of pneumococcal meningitis.
- These findings contribute to a better understanding of the disease and may guide the development of novel therapeutic strategies.
Abstract:
Streptococcus pneumoniae is responsible for diseases causing major global public health problems, including meningitis, pneumonia and septicaemia. Despite recent advances in antimicrobial therapy, pneumococcal meningitis remains a life-threatening disease. Furthermore, long-term sequelae are a major concern for survivors. Hence, a better understanding of the processes occurring in the central nervous system is crucial to the development of more effective management strategies. We used mass spectrometry based quantitative proteomics to identify protein changes in cerebrospinal fluid from children with Streptococcus pneumoniae infection, compared with children admitted to hospital with bacterial meningitis symptoms but negative diagnosis. Samples were analysed, by label free proteomics, in two independent cohorts (cohort 1: cases (n = 8) and hospital controls (n = 4); cohort 2: cases (n = 8), hospital controls (n = 8)). Over 200 human proteins were differentially expressed in each cohort, of which 65% were common to both. Proteins involved in the immune response and exosome signalling were significantly enriched in the infected samples. For a subset of proteins derived from the proteome analysis, we corroborated the proteomics data in a third cohort (hospital controls (n = 15), healthy controls (n = 5), cases (n = 20)) by automated quantitative western blotting, with excellent agreement with our proteomics findings. Proteomics data are available via ProteomeXchange with identifier PXD004219.
