In this project, we tried to use affinity-purification mass spectrometry (AP-MS) to study host-pathogen protein interaction, focusing initially on two major virulence factors of group A streptococcus (GAS), streptolysin O (SLO) and C5a peptidase (C5AP) with the immediate host microenvironment (human plasma or saliva); next centering on one major pathogenic host factor of GAS, human plasminogen (PLG) molecule with streptococcal cell-wall associate proteins (CAP) or secreted proteins (SP). Quantitative MS was performed in combination with interaction analysis to pinpoint the high-confidence interactive partner to the corresponding baits.