SarA and not σB is essential for biofilm development by Staphylococcus aureus

Staphylococcus aureus biofilm formation is associated with the production of the polysaccharide intercellular adhesin (PIA/PNAG), the product of the ica operon. The staphylococcal accessory regulator, SarA, is a central regulatory element that controls the production of S. aureus virulence factors. By screening a library of Tn917 insertions in a clinical S. aureus strain, we identified SarA as being essential for biofilm development. Non-polar mutations of sar A in four genetically unrelated S. aureus strains decreased PIA/PNAG production and completely impaired biofilm development, both in steady state and flow conditions via an agr -independent mechanism. Accordingly, real-time PCR showed that the mutation in the sar A gene resulted in downregulation of the ica operon transcription. We also demonstrated that complete deletion of sigma(B) did not affect PIA/PNAG production and biofilm formation, although it slightly decreased ica operon transcription. Furthermore, the sar A-sigma(B) double mutant showed a significant decrease of ica expression but an increase of PIA/PNAG production and biofilm formation compared to the sar A single mutant. We propose that SarA activates S. aureus development of biofilm by both enhancing the ica operon transcription and suppressing the transcription of either a protein involved in the turnover of PIA/PNAG or a repressor of its synthesis, whose expression would be sigma(B) -dependent.