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A High Throughput, Multiplexed and Targeted Proteomic CSF Assay to Quantify Neurodegenerative Biomarkers and Apolipoprotein E Isoforms Status
Published on: October 20, 2016
Enhanced microbiological evaluation of brain abscesses by proteomics-based techniques: a prospective cohort study
Nisarg Parmar1, Kautilya R Patel1, Madhusudhan Nagesh1
11Department of Neurosurgery.
Objective:
Microbiological analysis might not be able to identify the causative pathogen in one-third of brain abscess patients. Proteomics analysis of brain abscesses can aid in microbiological diagnosis. This could help tailor the antimicrobial therapy, give possible insights into the source of the abscess, and aid in developing targeted antimicrobial agents.
Methods:
This was a single-center prospective study including patients with brain abscess recruited over a 1-year period. Proteome-based analysis was used to identify the causative pathogen, and the results were compared using conventional microbiological analysis. The involved host proteins were identified and correlated with the abscess volume.
Results:
Thirty-four patients with brain abscesses were included. The mean volume of the abscess was 30.4 cm3. A pus sample was obtained by craniotomy excision (67.6% of cases), burr hole aspiration (17.6% of cases), or twist-drill craniostomy aspiration (14.7% of cases). Proteomics analysis was successful in 19 (55.9%) samples. The remaining samples were rejected during preprocessing due to technical/sampling issues. In total, 7331 proteins were identified from 19 samples, with a mean of 385 proteins (range 291-615 proteins) per sample. All patients except one were found to have polymicrobial infection based on proteomics analysis, with a median of 4 microorganisms per sample. The causative pathogen could be identified by microbiological analysis in 25 of 34 (73.5%) patients and in 15 of 19 (78.9%) patients with successful proteomics analysis. Staphylococcus aureus, Acinetobacter baumannii, and Escherichia coli were the most common microorganisms on proteomics analysis, whereas Streptococcus intermedius, Streptococcus constellatus, and S. aureus were the most common microorganisms on microbiological analysis. Microorganisms identified by microbiological analysis matched one of the results from proteomics analysis in 66.7% of patients. Of the inflammatory proteins identified, ferritin heavy chain, neutrophil collagenase isoform XI, proteasome subunit beta type-1, ferritin light chain isoform XI, proteasome subunit alpha type-6 isoform a, resistin precursor, and neutrophil defensin 1 isoform XI showed a positive correlation with abscess volume, whereas complement C3 preproprotein, serotransferrin isoform 1, and histone H2B type 1-D protein showed a negative correlation.
Conclusions:
Proteomics analysis suggests that most brain abscesses contain polymicrobial colonization, which underscores the importance of broad-spectrum antibiotics in their treatment. It can aid in diagnosis when conventional tests fail to isolate the pathogen and can provide deeper insights into microorganism-host interactions.
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