A Multi-Serotype Approach Clarifies the Catabolite Control Protein A Regulon in the Major Human Pathogen Group A Streptococcus

Sruti Debroy, Miguel Saldaña, Dante Travisany, Andrew Montano, Jessica Galloway-Peña, Nicola Horstmann, Hui Yao, Mauricio González, Alejandro Maass, Mauricio Latorre, Samuel A. Shelburne

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Article number32442
JournalScientific Reports
Volume6
DOIs
StatePublished - Sep 1 2016

ASJC Scopus subject areas

  • General

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