Distinct virulent network between healthcare- and community-associated Staphylococcus aureus based on proteomic analysis

Abstract

Background: Staphylococcus aureus (S. aureus or SA) is a leading cause of healthcare-associated (HA-) and community-associated (CA) infection. HA-SA isolates usually cause nosocomial pneumonia, bloodstream infections, catheter-related urinary tract infections, etc. On the other hand, CA-SA isolates usually cause highly fatal diseases, such as SSTIs as well as post influenza necrotic hemorrhagic pneumonia. The differences of the infection types are partially due to the unique characteristics between HA-SA and CA-SA isolates. For example, HA-SA isolates showed strong adherence to host epithelial cells, while CA-SA isolates displayed higher virulence due to the increased activity of the important quorum-sensing system accessory gene regulator (agr). Thus, the aim of this study was to characterize the proteomic difference between HA-SA and CA-SA lineage. Methods: In this study, the extracted peptides from those representative strains were analyzed by LC-MS/MS. The protein-protein interaction network was constructed by bioinformatics and their expressions were verified by RT-PCR and Western blot. Results: We demonstrated that Agr system (AgrA and AgrC) and its interactive factors (PhoP, SrrB, YycG, SarX, SigB and ClpP) based on the protein-protein interaction network were expressed significantly higher in the epidemic Chinese CA-SA lineage ST398 compared to HA-SA lineage ST239 by LC-MS/MS. We further verified the increased transcription of all these genes in ST398 by RT-PCR, suggesting that the higher expression of these genes/proteins probably play role in the acute infection of CA-SA. Moreover, surface-related proteins (FnbpA, SpA, Atl, ClfA, IsaA, IsaB, LtaS, SsaA and Cna) that are repressed by the Agr system have significantly higher expression in the epidemic Chinese HA-SA clone ST239 in comparison to CA-SA lineage ST398 by LC-MS/MS. Furthermore, we confirmed the significantly increased expression of two important adhesive proteins (Atl and ClfA) in ST239 by Western blot, which may contribute to the durative infection of HA-SA. Conclusion: The results suggest that the different proteomic profile, at least partially, contribute to the pathogenic differences between HA-SA and CA-SA.