Hydrogen sulfide (H2S) is ubiquitously distributed in the human body and involved as signaling molecule in a wide range of physiological processes. Despite its function as a gaseous signaling molecule, H2S is primarily known for its toxicity, which mainly arises from its ability to inhibit the respiratory chain. Thus many microorganisms, including the opportunistic pathogen S. aureus, protect themselves from these effects. The genome of S. aureus contains the cst gene cluster, consisting of the genes tauE, cstR, cstA, cstB and sqr. It is reported to be involved in the detoxification of sulfide. The proposed detoxification process is initiated by the oxidation of sulfide by means of the sulfide:quinone oxidoreductase (SQR), followed by the stepwise conversion into sulfite by CstA and CstB and the subsequent export of sulfite by TauE.

Phylogenetic analyses revealed that the cst operon is widely distributed among staphylococci. However, we found that the presence of the sqr in the cst operon is essentially limited to S. aureus indicating that the function of the core cst operon in staphylococci is not the detoxification of H2S. Phenotypical analyses of a comprehensive set of cst deletion and complementation mutants and numerous clinical and laboratory derived strains, revealed the core cst gene cluster to be essential for the detoxification of polysulfides rather than H2S. In addition, we found a partial duplication of the core cst gene cluster associated with SCCmec in clinically relevant S. aureus (MRSA). Moreover, our studies revealed this cluster to be functional and to confer higher polysulfide tolerance to MRSA.