Furthermore, our more recent results suggest that SigB is involved in the emergence of SCVs under aminoglycoside pressure [20], which suggests that the appearance of SCVs may be a regulated process influenced by environmental cues. Our current hypothesis is that SigB plays an important role in the establishment of chronic and difficult-to-treat S. aureus infections. SigB is involved

in the check details response to environmental stresses such as during stationary phase, heat exposure and change in osmotic pressure [21]. Moreover, the activity of SigB positively influences the expression of several cell-surface proteins whereas it down-regulates a variety of selleck kinase inhibitor toxins [22], which suggest an important role for SigB in pathogenesis. The effect

of SigB on virulence gene expression can be direct or indirect, since the genes regulated by SigB also include at least another global regulator of virulence, sarA (Staphylococcal accessory regulator) [22, 23]. SarA modulates the expression of several virulence factors either by stimulating RNAIII transcription or by pathway(s) independent of the agr (accessory gene regulator) system [24]. In turn, Selleckchem Sotrastaurin it is proposed that the quorum-sensing agr system controls the transition from colonization to dissemination by up-regulating the expression of several exotoxins and proteolytic enzymes and by repressing the expression of cell-surface proteins involved in colonization [25]. agr medroxyprogesterone [26], SigB [27, 28] and SarA [29] are known to influence the formation of biofilms by S. aureus. At least two different mechanisms of biofilm formation exist in S. aureus [26, 29–33]. The first mechanism implies the production of the polysaccharide intercellular adhesin (PIA), which requires the ica gene cluster, whereas the second mechanism is ica-independent. With opposite effects, SarA and agr are both involved in the ica-independent mechanism of biofilm formation. SarA is thought

to be indirectly required for the initial attachment step to biological matrices [29, 32, 33], while agr is controlling the dispersal process of biofilms [26]. Recently, Lauderdale et al. [30] have shown that SigB is an essential regulator of the ica-independent biofilm formation and suggested that SigB acts upstream of the agr system, allowing the formation of biofilm to be regulated as a function of environmental factors. Noteworthy, biofilms have been linked to chronic infections, especially in the case of those found in the airways of CF patients [1, 34], and an increased formation of biofilms has been associated with the SCV phenotype [20, 35]. The aim of this study was to investigate the association between the activity of SigB, the emergence of SCVs and biofilm production in S.