Veterinary and Biomedical Sciences, Department of
Document Type
Article
Date of this Version
2014
Citation
Published in The Journal of Biological Chemistry 289 (2014), pp. 29701-29711; doi: 10.1074/jbc.M114.584979
Abstract
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 α-toxin; and psmα, encoding the phenol-soluble modulin cluster α. Electrophoretic mobility shift assays demonstrated that CcpE binds to the hla promoter. Mice challenged with S. aureus strain Newman or its isogenic ΔccpE derivative revealed increased disease severity in the ΔccpE 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.
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Animal Diseases Commons, Cell and Developmental Biology Commons, Respiratory Tract Diseases Commons, Veterinary Infectious Diseases Commons, Veterinary Microbiology and Immunobiology Commons, Veterinary Pathology and Pathobiology Commons
Comments
Copyright © 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Used by permission.