Comparison of the plasma proteome during gram-positive and gram-negative pneumonia in mice

Abstract Introduction: We hypothesized that the mouse plasma proteome during Gram-positive pneumonia would be similar to that of Gram-negative pneumonia when the infectious agents are used in doses that cause similar mortality rates. Methods: Male C57/BL6 mice underwent intratracheal (i.t.). injections of either P. aeruginosa or S. pneumoniae at doses that resulted in 80–90% seven-day mortality; control mice received i.t. normal saline alone. Plasma was collected twenty-four hours after infection. Multiplex fluorescent 2-D gel electrophoresis was used to compare the plasma protein compositions in two replicates. Differentially expressed gel features were identified based on comparison to gel images of plasma from animals subjected to intra-abdominal sepsis (cecal ligation and puncture, CLP) or de novo by tandem mass spectrometry. Results: Approximately 1200 gel features were detected in each replicate. The pattern of protein abundance clearly distinguishes P. aeruginosa, while more subtle variations separate S. pneumoniae from i.t. saline. As an example, the most prominent differences between the plasma samples are shown in the Table. TablePlasma Protein Abundance Fold Change, Relative to i.t. Saline Challenge (Control)Apolipo- protein A-1alpha-1 Acid Glyco- proteinHapto- globinalpha- fibrinogenbeta- fibrinogenP. aeruginosa−162.7 (ns)−9.4−5.3−5.7S. pneumoniae−1.8 (ns)3.8−1.1 (ns)−1.1 (ns)−1.6 (ns)All changes p Conclusions: Here we present the first proteomic analysis of the mouse plasma acute phase response to pneumonia and further compare Gram-positive to Gram-negative disease. These profiles are distinct, suggesting that the host response to pulmonary sepsis at the level of the plasma proteome may be diagnostic for these infectious agents.