Abstract: Novel strains of Staphylococcus aureus and uses thereof. The invention provides mutant strains of S. aureus devoid of all non-essential two-component signal systems (TCSs) and even the essential walKR system, the intermediate mutants devoid of a number of TCSs and their uses as research and biotechnological platform. The mutants devoid of all non-essential TCSs are viable, stable under laboratory growing conditions, genetically manageable and capable to express heterologous proteins. Having them allows individual analysis and targeting of each TCS, its individual complementation and obtaining information about the sensing systems that can be useful for biotechnological applications based or directed to S. aureus, such as the identification of novel antimicrobials.