PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of plosonePLoS OneView this ArticleSubmit to PLoSGet E-mail AlertsContact UsPublic Library of Science (PLoS)
 
PLoS One. 2012; 7(9): e44766.
Published online Sep 13, 2012. doi:  10.1371/journal.pone.0044766
PMCID: PMC3441419
The Redox-Sensing Regulator Rex Modulates Central Carbon Metabolism, Stress Tolerance Response and Biofilm Formation by Streptococcus mutans
Jacob P. Bitoun,1 Sumei Liao,1 Xin Yao,1 Gary G. Xie,2 and Zezhang T. Wen1,3*
1Department of Oral and Craniofacial Biology, School of Dentistry, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America
2Biology and Bioinformatics, Los Alamos National Laboratory, New Mexico, United States of America
3Department of Microbiology, Immunology, and Parasitology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America
Indranil Biswas, Editor
University of Kansas Medical Center, United States of America
* E-mail: zwen/at/lsuhsc.edu
Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: JPB ZTW. Performed the experiments: JPB SL XY GGX. Analyzed the data: JPB ZTW. Contributed reagents/materials/analysis tools: GGX ZTW. Wrote the paper: JPB ZTW.
Received March 30, 2012; Accepted August 6, 2012.
Abstract
The Rex repressor has been implicated in regulation of central carbon and energy metabolism in Gram-positive bacteria. We have previously shown that Streptococcus mutans, the primary causative agent of dental caries, alters its transcriptome upon Rex-deficiency and renders S. mutans to have increased susceptibility to oxidative stress, aberrations in glucan production, and poor biofilm formation. In this study, we showed that rex in S. mutans is co-transcribed as an operon with downstream guaA, encoding a putative glutamine amidotransferase. Electrophoretic mobility shift assays showed that recombinant Rex bound promoters of target genes avidly and specifically, including those down-regulated in response to Rex-deficiency, and that the ability of recombinant Rex to bind to selected promoters was modulated by NADH and NAD+. Results suggest that Rex in S. mutans can function as an activator in response to intracellular NADH/NAD+ level, although the exact binding site for activator Rex remains unclear. Consistent with a role in oxidative stress tolerance, hydrogen peroxide challenge assays showed that the Rex-deficient mutant, TW239, and the Rex/GuaA double mutant, JB314, were more susceptible to hydrogen peroxide killing than the wildtype, UA159. Relative to UA159, JB314 displayed major defects in biofilm formation, with a decrease of more than 50-fold in biomass after 48-hours. Collectively, these results further suggest that Rex in S. mutans regulates fermentation pathways, oxidative stress tolerance, and biofilm formation in response to intracellular NADH/NAD+ level. Current effort is being directed to further investigation of the role of GuaA in S. mutans cellular physiology.
Articles from PLoS ONE are provided here courtesy of
Public Library of Science