Host macrophage modulation of cell death and related pathways during early MSSA and MRSA infection

Background MRSA is one of the major human and veterinary pathogen responsible of multiple serious infections and outbreaks Methicillin-resistant Staphylococcus aureus (MRSA) resistance is due to the acquisition by Methicillin-susceptible (MSSA) strains of the mobile gene segment mec (SCCmec). Moreover, few investigations have been made on MSSA despite the importance in resistance acquisition and as source of infection. The aim of this project is the investigation of the host proteome modulation during strain-specific infection at different time-points using a quantitative label-free approach. Methods Protein expression changes at 1h and 2h in MRSA and MSSA infected THP1 cells have been detected using a label free approach. Three biological replicates has been analysed in quadruplicate using a SYNAPT G2-Si (Waters) applying the MSE data acquisition strategy coupled to IPA (Qiagen) bioinformatics analysis Results. Label free MSE led to identification of 110 and 157 differentially expressed macrophage proteins (p<0.05) after 1h and 2h of infection, respectively. Of 157 macrophage proteins 103 of them have been found exclusively downregulated in mrsa infection after 2h and 33 and 21 respectively down and up regulated in MSSA infected THP1 after 2h. Ingenuity pathway analysis highlighted several canonical pathways and bio-functions differentially regulated during the infection stage. In particular, apoptosis seems to be inhibited at 1h of infection in MSSA infected THP-1 compared to the other time points and to MRSA. Moreover, on the basis of the host protein modulation there is a possible evidence of early pathogen exit from host cells in the MSSA infection. Conclusions Proteomic data obtained in this work could provide new knowledge