The proteome of pus from human brain abscesses: host-derived neurotoxic proteins and the cell-type diversity of CNS pus

OBJECTIVEWhat determines the extent of tissue destruction during brain abscess formation is not known. Pyogenic brain infections cause destruction of brain tissue that greatly exceeds the area occupied by microbes, as seen in experimental studies, pointing to cytotoxic factors other than microbes in pus. This study examined whether brain abscess pus contains cytotoxic proteins that might explain the extent of tissue destruction.METHODSPus proteins from 20 human brain abscesses and, for comparison, 7 subdural empyemas were analyzed by proteomics mass spectrometry. Tissue destruction was determined from brain abscess volumes as measured by MRI.RESULTSBrain abscess volume correlated with extracellular pus levels of antibacterial proteins from neutrophils and macrophages: myeloperoxidase (r = 0.64), azurocidin (r = 0.61), lactotransferrin (r = 0.57), and cathelicidin (r = 0.52) (p values 0.002–0.018), suggesting an association between leukocytic activity and tissue damage. In contrast, perfringolysin O, a cyt...