A Multi-Serotype Approach Clarifies the Catabolite Control Protein A Regulon in the Major Human Pathogen Group A Streptococcus.
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Catabolite control protein A (CcpA) is a highly conserved, master regulator of carbon source utilization in gram-positive bacteria, but the CcpA regulon remains ill-defined. In this study we aimed to clarify the CcpA regulon by determining the impact of CcpA-inactivation on the virulence and transcriptome of three distinct serotypes of the major human pathogen Group A Streptococcus (GAS). CcpA-inactivation significantly decreased GAS virulence in a broad array of animal challenge models consistent with the idea that CcpA is critical to gram-positive bacterial pathogenesis. Via comparative transcriptomics, we established that the GAS CcpA core regulon is enriched for highly conserved CcpA binding motifs (i.e. cre sites). Conversely, strain-specific differences in the CcpA transcriptome seems to consist primarily of affected secondary networks. Refinement of cre site composition via analysis of the core regulon facilitated development of a modified cre consensus that shows promise for improved prediction of CcpA targets in other medically relevant gram-positive pathogens.
author list (cited authors)
DebRoy, S., Saldaa, M., Travisany, D., Montano, A., Galloway-Pea, J., Horstmann, N., ... Shelburne, S. A.
complete list of authors
DebRoy, Sruti||Saldaña, Miguel||Travisany, Dante||Montano, Andrew||Galloway-Peña, Jessica||Horstmann, Nicola||Yao, Hui||González, Mauricio||Maass, Alejandro||Latorre, Mauricio||Shelburne, Samuel A