The Catabolite Control Protein E (CcpE) Affects Virulence Determinant Production and Pathogenesis of Staphylococcus aureus

Background: Carbon metabolism and virulence are often linked in pathogenic bacteria. Results: Deletion of the catabolite control protein E (CcpE) affects the expression of virulence factors and pathogenicity of Staphylococcus aureus. Conclusion: Our data suggest that CcpE acts as an attenuator of virulence in S. aureus.Significance: CcpE may serve to link S. aureus nutritional status to virulence determinant biosynthesis. Carbon metabolism and virulence determinant production are often linked in pathogenic bacteria, and several regulatory elements have been reported to mediate this linkage in Staphylococcus aureus. Previously, we described a novel protein, catabolite control protein E (CcpE) that functions as a regulator of the tricarboxylic acid cycle. Here we demonstrate that CcpE also regulates virulence determinant biosynthesis and pathogenesis. Specifically, deletion of ccpE in S. aureus strain Newman revealed that CcpE affects transcription of virulence factors such as capA, the first gene in the capsule biosynthetic operon; hla, encoding -toxin; and psm, encoding the phenol-soluble modulin cluster . Electrophoretic mobility shift assays demonstrated that CcpE binds to the hla promoter. Mice challenged with S. aureus strain Newman or its isogenic ccpE derivative revealed increased disease severity in the ccpE mutant using two animal models; an acute lung infection model and a skin infection model. Complementation of the mutant with the ccpE wild-type allele restored all phenotypes, demonstrating that CcpE is negative regulator of virulence in S. aureus.