A Multi-Serotype Approach Clarifies the Catabolite Control Protein A Regulon in the Major Human Pathogen Group A Streptococcus.
Sci Rep, 2016/09/01;6:32442.
DebRoy S[1], Saldaña M[1], Travisany D[2, 3], Montano A[1], Galloway-Peña J[1], Horstmann N[1], Yao H[4], González M[3, 5], Maass A[2, 3, 6], Latorre M[2, 3, 5], Shelburne SA[1, 7]
Affiliations
PMID: 27580596DOI: 10.1038/srep32442
Impact factor: 4.996
Abstract
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.
MeSH terms
Animals; Bacterial Proteins; Female; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Humans; Mice; Nucleotide Motifs; Regulon; Repressor Proteins; Serogroup; Streptococcal Infections; Streptococcus pyogenes; Survival Analysis; Transcriptome; Virulence
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