title: The redox-sensing regulator Rex modulates central carbon metabolism, stress tolerance response and biofilm formation by Streptococcus mutans.
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.
authors.affiliation: Department of Oral and Craniofacial Biology, School of Dentistry, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America.
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Bitoun
authors.forename: Sumei
authors.initials: S
authors.lastname: Liao
authors.forename: Xin
authors.initials: X
authors.lastname: Yao
authors.forename: Gary G
authors.initials: GG
authors.lastname: Xie
authors.forename: Zezhang T
authors.initials: ZT
authors.lastname: Wen
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development*; D002244:Carbon / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics / Q000502:physiology; D010084:Oxidation-Reduction; D013295:Streptococcus mutans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D002244:Carbon