title: A Multi-Serotype Approach Clarifies the Catabolite Control Protein A Regulon in the Major Human Pathogen Group A Streptococcus.
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.
authors: Department of Infectious Diseases, MD Anderson Cancer Center, Houston, Texas, USA.
authors: Sruti
authors: S
authors: DebRoy
authors: Department of Infectious Diseases, MD Anderson Cancer Center, Houston, Texas, USA.
authors: Miguel
authors: M
authors: Saldaña
authors: Mathomics, Center for Mathematical Modeling, Universidad de Chile, Beauchef 851, 7th Floor, Santiago, Chile.|Center for Genome Regulation (Fondap 15090007), Universidad de Chile, Blanco Encalada 2085, Santiago, Chile.
authors: Dante
authors: D
authors: Travisany
authors: Department of Infectious Diseases, MD Anderson Cancer Center, Houston, Texas, USA.
authors: Andrew
authors: A
authors: Montano
authors: Department of Infectious Diseases, MD Anderson Cancer Center, Houston, Texas, USA.
authors: Jessica
authors: J
authors: Galloway-Peña
authors: Department of Infectious Diseases, MD Anderson Cancer Center, Houston, Texas, USA.
authors: Nicola
authors: N
authors: Horstmann
authors: Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, Texas, USA.
authors: Hui
authors: H
authors: Yao
authors: Center for Genome Regulation (Fondap 15090007), Universidad de Chile, Blanco Encalada 2085, Santiago, Chile.|Laboratorio de Bioinformática y Expresión Génica, INTA, Universidad de Chile, El Líbano 5524, Macul, Santiago, Chile.
authors: Mauricio
authors: M
authors: González
authors: Mathomics, Center for Mathematical Modeling, Universidad de Chile, Beauchef 851, 7th Floor, Santiago, Chile.|Center for Genome Regulation (Fondap 15090007), Universidad de Chile, Blanco Encalada 2085, Santiago, Chile.|Department of Mathematical Engineering, Universidad de Chile, Beauchef 851, 5th Floor, Santiago, Chile.
authors: Alejandro
authors: A
authors: Maass
authors: Mathomics, Center for Mathematical Modeling, Universidad de Chile, Beauchef 851, 7th Floor, Santiago, Chile.|Center for Genome Regulation (Fondap 15090007), Universidad de Chile, Blanco Encalada 2085, Santiago, Chile.|Laboratorio de Bioinformática y Expresión Génica, INTA, Universidad de Chile, El Líbano 5524, Macul, Santiago, Chile.
authors: Mauricio
authors: M
authors: Latorre
authors: Department of Infectious Diseases, MD Anderson Cancer Center, Houston, Texas, USA.|Department of Genomic Medicine, MD Anderson Cancer Center, Houston, Texas, USA.
authors: Samuel A
authors: SA
authors: Shelburne
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D051379:Mice; D059372:Nucleotide Motifs; D018085:Regulon; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D065288:Serogroup; D013290:Streptococcal Infections / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D013297:Streptococcus pyogenes / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D016019:Survival Analysis; D059467:Transcriptome; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D012097:Repressor Proteins; C069286:catabolite control proteins, bacteria