Niche-specific contribution to streptococcal virulence of a MalR-regulated carbohydrate binding protein.

Published

Journal Article

Low G+C Gram-positive bacteria typically contain multiple LacI/GalR regulator family members, which often have highly similar amino-terminal DNA binding domains, suggesting significant overlap in target DNA sequences. The LacI/GalR family regulator catabolite control protein A (CcpA) is a global regulator of the Group A Streptococcus (GAS) transcriptome and contributes to GAS virulence in diverse infection sites. Herein, we studied the role of the maltose repressor (MalR), another LacI/GalR family member, in GAS global gene expression and virulence. MalR inactivation reduced GAS colonization of the mouse oropharynx but did not detrimentally affect invasive infection. The MalR transcriptome was limited to only 25 genes, and a highly conserved MalR DNA-binding sequence was identified. Variation of the MalR binding sequence significantly reduced MalR binding in vitro. In contrast, CcpA bound to the same DNA sequences as MalR but tolerated variation in the promoter sequences with minimal change in binding affinity. Inactivation of pulA, a MalR regulated gene which encodes a cell surface carbohydrate binding protein, significantly reduced GAS human epithelial cell adhesion and mouse oropharyngeal colonization but did not affect GAS invasive disease. These data delineate a molecular mechanism by which hierarchical regulation of carbon source utilization influences bacterial pathogenesis in a site-specific fashion.

Full Text

Duke Authors

Cited Authors

  • Shelburne, SA; Sahasrobhajane, P; Suber, B; Keith, DB; Davenport, MT; Horstmann, N; Kumaraswami, M; Olsen, RJ; Brennan, RG; Musser, JM

Published Date

  • July 2011

Published In

Volume / Issue

  • 81 / 2

Start / End Page

  • 500 - 514

PubMed ID

  • 21645132

Pubmed Central ID

  • 21645132

Electronic International Standard Serial Number (EISSN)

  • 1365-2958

Digital Object Identifier (DOI)

  • 10.1111/j.1365-2958.2011.07708.x

Language

  • eng

Conference Location

  • England