MsaB and CodY Interact To Regulate Staphylococcus aureus Capsule in a Nutrient-Dependent Manner

has a complex regulatory network for controlling the production of capsule polysaccharide. In , 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 the promoter 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 the promoter in a nutrient-dependent manner. We observed that and interact in a complex fashion to regulate capsule production. However, we confirmed that does not bind directly. We also defined the regulatory relationship between and CodY. When nutrients (branched-chain amino acids) are abundant, CodY binds to the promoter region of the operon and represses its transcription. However, when nutrient concentrations decrease, MsaB, rather than CodY, binds to the promoter. Binding of MsaB to the promoter activates transcription of the operon. We hypothesize that this same mechanism may be used by to regulate other virulence factors. Findings from this study define the mechanism of regulation of capsule production in Specifically, we show that two key regulators, MsaB and CodY, coordinate their functions to control the expression of capsule in response to nutrients. fine-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.