Distinct Regulatory Role of Carbon Catabolite Protein A (CcpA) in Oral Streptococcal spxB Expression

Pyruvate oxidase (SpxB)-dependent H2 O2 production is under the control of carbon catabolite protein A (CcpA) in the oral speciesStreptococcus sanguinis andStreptococcus gordonii . Interestingly, both species react differently to the presence of the preferred carbohydrate source glucose.S. gordonii CcpA-dependent regulation ofspxB follows classical carbon catabolite repression. Conversely,spxB expression inS. sanguinis is not influenced by glucose but is repressed by CcpA. Here, we constructed strains expressing the heterologous versions of CcpA or thespxB promoter region to learn if the distinct regulation ofspxB expression is transferable fromS. gordonii toS. sanguinis and vice versa. While cross-species binding of CcpA to thespxB promoter is conservedin vitro , we were unable to swap the species-specific regulation. This suggests that a regulatory mechanism upstream of CcpA most likely is responsible for the observed difference inspxB expression. Moreover, the overall ecological significance of differentialspxB regulation in the presence of various glucose concentrations was tested with additional oral streptococcus isolates and demonstrated that carbohydrate-dependent and carbohydrate-independent mechanisms exist to control expression ofspxB in the oral biofilm. Overall, our data demonstrate the unexpected finding that metabolic pathways between two closely related oral streptococcal species can be regulated differently despite an exceptionally high DNA sequence identity.IMPORTANCE Polymicrobial diseases are the result of interactions among the residential microbes, which can lead to a dysbiotic community.Streptococcus sanguinis andStreptococcus gordonii are considered commensal species that are present in the healthy dental biofilm. Both species are able to produce significant amounts of H2 O2 via the enzymatic action of the pyruvate oxidase SpxB. H2 O2 is able to inhibit species associated with oral diseases. SpxB and its gene-regulatory elements present in both species are highly conserved. Nonetheless, a differential response to the presence of glucose was observed. Here, we investigate the mechanisms that lead to this differential response. Detailed knowledge of the regulatory mechanisms will aid in a better understanding of oral disease development and how to prevent dysbiosis.