Effects of Subminimum Inhibitory Concentrations of Antibiotics on thePasteurella multocidaProteome: A Systems Approach

To identify key regulators of subminimum inhibitory concentration (sub-MIC) antibiotic response in thePasteurella multocidaproteome, we applied systems approaches. Using 2D-LC-ESI-MS2, we achieved 53% proteome coverage. To study the differential protein expression in response to sub-MIC antibiotics in the context of protein interaction networks, we inferredP. multocidaPm70 protein interaction network from orthologous proteins. We then overlaid the differential protein expression data onto theP. multocidaprotein interaction network to study the bacterial response. We identified proteins that could enhance antimicrobial activity. Overall compensatory response to antibiotics was characterized by altered expression of proteins involved in purine metabolism, stress response, and cell envelope permeability.