Distinct time-resolved roles for two catabolite-sensing pathways during Streptococcus pyogenes infection.
Infect Immun
; 79(2): 812-21, 2011 Feb.
Article
em En
| MEDLINE
| ID: mdl-21098101
ABSTRACT
Many Gram-positive pathogens link the expression of virulence genes to the presence of carbon source substrates using overlapping pathways for global control of carbon catabolite regulation. However, how these pathways are integrated to control the behavior of the transcriptome in time- and compartment-specific patterns is typically not well understood. In the present study, global transcriptome profiling was used to determine the extent to which glucose alters gene expression in Streptococcus pyogenes (group A streptococcus) and the contributions of the CcpA and LacD.1 catabolite control pathways to the regulation of this response in vitro. This analysis revealed that the expression of as many as 15% of the genes examined was regulated and that CcpA and LacD.1 together contribute to the regulation of 60% of this subset. However, numerous patterns were observed, including both CcpA- and LacD.1-specific and independent regulation, coregulation, and regulation of genes by these pathways independently of glucose. In addition, CcpA and LacD.1 had antagonistic effects on most coregulated genes. To resolve the roles of these regulators during infection, the expression of selected transcripts representative of different regulatory patterns was examined in a murine model of soft tissue infection. This revealed distinct patterns of misregulation with respect to time in CcpA(-) versus LacD.1(-) mutants. Taken together, these data support an important role for carbohydrate in the regulation of the transcriptome in tissue and suggest that the CcpA and LacD.1 pathways are organized to function at different times during the course of an infection.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções Estreptocócicas
/
Streptococcus pyogenes
/
Proteínas de Bactérias
/
Infecções dos Tecidos Moles
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Infect Immun
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos