MsaB and CodY Interact To RegulateStaphylococcus aureusCapsule in a Nutrient-Dependent Manner
ABSTRACTStaphylococcus aureushas a complex regulatory network for controlling the production of capsule polysaccharide. InS. aureus, capsule production is controlled by several regulators in response to various environmental stimuli. Previously, we described MsaB as a new regulator that specifically binds to thecappromoter in a growth phase- or nutrient-dependent manner. In addition to MsaB, several other regulators have also been shown to bind the same region. In this study, we examined the interactions between MsaB and other nutrient-sensing regulators (CodY and CcpE) with respect to binding to thecappromoter in a nutrient-dependent manner. We observed thatmsaABCRandccpEinteract in a complex fashion to regulate capsule production. However, we confirmed thatccpEdoes not bindcapdirectly. We also defined the regulatory relationship betweenmsaABCRand CodY. When nutrients (branched-chain amino acids) are abundant, CodY binds to the promoter region of thecapoperon and represses its transcription. However, when nutrient concentrations decrease, MsaB, rather than CodY, binds to thecappromoter. Binding of MsaB to thecappromoter activates transcription of thecapoperon. We hypothesize that this same mechanism may be used byS. aureusto regulate other virulence factors.IMPORTANCEFindings from this study define the mechanism of regulation of capsule production inStaphylococcus aureus. Specifically, we show that two key regulators, MsaB and CodY, coordinate their functions to control the expression of capsule in response to nutrients.S. aureusfine-tunes the production of capsule by coordinating the activity of several regulators and by sensing nutrient levels. This study demonstrates the importance of incorporating multiple inputs prior to the expression of costly virulence factors, such as capsule.