Heme Sensor System Potential Player in Methicillin Resistant Staphylococcus aureus Biofilm formation

Staphylococcus aureus is a notorious pathogen responsible for life threatening diseases. It is known to acquire resistance to antimicrobials rapidly and reduces treatment efficacy by forming rigid biofilms. Regulation of biofilm synthesis and to a large extent antimicrobial resistance, is mediated through Two-component system (TCS) signal transduction machinery in this bacterium. S. aureus contains 16 TCSs responsible for sensing and adapting to stress conditions. Till date, the exact molecular mechanism responsible for resistance, especially in methicillin resistant S. aureus (MRSA) has not been completely defined. Our study traces the complete gene expression profile of the two-component system response regulators in both planktonic as well as the biofilm mode of clinical MRSA strains. A distinct expression pattern of the heme sensing response regulator hssR was observed in the MRSA-COL strain as compared to the clinical MRSA isolate 41301, where the later showed downregulation by 3.3 folds under antibiotic stress. The expression analysis in the biofilm mode of the MRSA strain also suggested 25-fold upregulation of hssR. Six other clinical MRSA strains also showed significant upregulation of hssR in biofilm mode of growth. Our data indicates for the first time that hssR is a key regulator of biofilm synthesis in MRSA strains.