Meta-Analysis of Human Molecular Responses to Staphylococcus Aureus Components

Objective: This study is aimed to identify genes and pathways that are upregulated or downregulated by Staphylococcus aureus components using meta-analysis.Study Design: Meta-analysis of microarray Data.Place and Duration of Study: The study was conducted at R.O. Perelman Department of Dermatology, NYU Langone Medical Center, New York, USA, from January 2015 to March 2015.Materials and Methods: Public repository “GEO Datasets” was searched using key term “Staphylococcus aureus” for data sets covering effects of S. aureus infection in Homo sapiens cells. Meta-analysis was performed using microarray data for immune cell responses to S. aureus components and analyzed using RankProd, RMAExpress, and DAVID software. Results: The secreted factors from biofilm and planktonic cultures predominantly induce adaptive immune process and suppress mitotic cell cycle. The biofilms conditioned media treated keratinocytes upregulate anti-apoptosis genes and immunity while planktonic cultures conditioned media treated keratinocytes upregulate cell cycle as major cytoprotective process. Similar to the secreted factors from S. aureus cultures, superantigens induce adaptive immunity and suppress innate immunity in challenged cells. S. aureus components Panton Valentine Leukocidin (PVL) and iPVL induce adaptive immune system as a defensive mechanism. Importantly, these S. aureus components increased microbicidal activity in host cells. Conclusion: PVL could be a potential priming agent for myeloid cells against virulent S. aureus infections. Further investigations into bactericidal ability of PVL will provide efficient therapy against community-associated Meticillin-resistant Staphylococcus aureus (CA-MRSA) infections.