title: In vitro manganese-dependent cross-talk between Streptococcus mutans VicK and GcrR: implications for overlapping stress response pathways.
abstract: Streptococcus mutans, a major acidogenic component of the dental plaque biofilm, has a key role in caries etiology. Previously, we demonstrated that the VicRK two-component signal transduction system modulates biofilm formation, oxidative stress and acid tolerance responses in S. mutans. Using in vitro phosphorylation assays, here we demonstrate for the first time, that in addition to activating its cognate response regulator protein, the sensor kinase, VicK can transphosphorylate a non-cognate stress regulatory response regulator, GcrR, in the presence of manganese. Manganese is an important micronutrient that has been previously correlated with caries incidence, and which serves as an effector of SloR-mediated metalloregulation in S. mutans. Our findings supporting regulatory effects of manganese on the VicRK, GcrR and SloR, and the cross-regulatory networks formed by these components are more complex than previously appreciated. Using DNaseI footprinting we observed overlapping DNA binding specificities for VicR and GcrR in native promoters, consistent with these proteins being part of the same transcriptional regulon. Our results also support a role for SloR as a positive regulator of the vicRK two component signaling system, since its transcription was drastically reduced in a SloR-deficient mutant. These findings demonstrate the regulatory complexities observed with the S. mutans manganese-dependent response, which involves cross-talk between non-cognate signal transduction systems (VicRK and GcrR) to modulate stress response pathways.
authors.affiliation: Division of Biomedical Sciences at the Herman Ostrow School of Dentistry of the University of Southern California, Los Angeles, California, United States of America.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Downey
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America.
authors.forename: Lauren
authors.initials: L
authors.lastname: Mashburn-Warren
authors.affiliation: Division of Biomedical Sciences at the Herman Ostrow School of Dentistry of the University of Southern California, Los Angeles, California, United States of America.
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Ayala
authors.affiliation: Dental Research Institute, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Dilani B
authors.initials: DB
authors.lastname: Senadheera
authors.affiliation: Middlebury College, Department of Biology, Middlebury, Vermont, United States of America.
authors.forename: Whitney K
authors.initials: WK
authors.lastname: Hendrickson
authors.affiliation: Middlebury College, Department of Biology, Middlebury, Vermont, United States of America.
authors.forename: Lathan W
authors.initials: LW
authors.lastname: McCall
authors.affiliation: Middlebury College, Department of Biology, Middlebury, Vermont, United States of America.
authors.forename: Julie G
authors.initials: JG
authors.lastname: Sweet
authors.affiliation: Dental Research Institute, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Dennis G
authors.initials: DG
authors.lastname: Cvitkovitch
authors.affiliation: Middlebury College, Department of Biology, Middlebury, Vermont, United States of America.
authors.forename: Grace A
authors.initials: GA
authors.lastname: Spatafora
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Goodman
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D008345:Manganese / Q000378:metabolism*; D009154:Mutation; D018085:Regulon; D015398:Signal Transduction; D013295:Streptococcus mutans / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D008345:Manganese