Staphylococcus aureus can cause a wide variety of diseases, which are attributed to its large repertoire of virulence factors, many of which are under the control of two component sensing systems (TCS). These systems allow the pathogen to alter and regulate its gene expression profile under the environmental stimuli. A simple TCS system is composed of a membrane associated histidine kinase and response regulator which is mainly present in cytosol. There is a total of sixteen such systems in Staphylococcus aureus which are involved in diverse signaling cascades including response to antimicrobial agents, nutrient sensing, chemotaxis, virulent gene regulation and biofilm formations. Most of these systems are interlinked and influence each other to regulate virulence profile of the pathogen. In this study, we summarize our current understanding of these systems and their different component in methicillin resistant Staphylococcus aureus which will have important implications in structure-based approaches for designing novel class of small molecule inhibitors to combat Staphylococcal infections.

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