title: Streptococcus mutans NADH oxidase lies at the intersection of overlapping regulons controlled by oxygen and NAD+ levels.
abstract: NADH oxidase (Nox, encoded by nox) is a flavin-containing enzyme used by the oral pathogen Streptococcus mutans to reduce diatomic oxygen to water while oxidizing NADH to NAD(+). The critical nature of Nox is 2-fold: it serves to regenerate NAD(+), a carbon cycle metabolite, and to reduce intracellular oxygen, preventing formation of destructive reactive oxygen species (ROS). As oxygen and NAD(+) have been shown to modulate the activity of the global transcription factors Spx and Rex, respectively, Nox is potentially poised at a critical junction of two stress regulons. In this study, microarray data showed that either addition of oxygen or loss of nox resulted in altered expression of genes involved in energy metabolism and transport and the upregulation of genes encoding ROS-metabolizing enzymes. Loss of nox also resulted in upregulation of several genes encoding transcription factors and signaling molecules, including the redox-sensing regulator gene rex. Characterization of the nox promoter revealed that nox was regulated by oxygen, through SpxA, and by Rex. These data suggest a regulatory loop in which the roles of nox in reduction of oxygen and regeneration of NAD(+) affect the activity levels of Spx and Rex, respectively, and their regulons, which control several genes, including nox, crucial to growth of S. mutans under conditions of oxidative stress.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Baker
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Derr
authors.affiliation: Center for Oral Biology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
authors.forename: K
authors.initials: K
authors.lastname: Karuppaiah
authors.affiliation: Center for Oral Biology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: MacGilvray
authors.affiliation: Center for Oral Biology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Kajfasz
authors.affiliation: Center for Oral Biology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Faustoferri
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
authors.forename: I
authors.initials: I
authors.lastname: Rivera-Ramos
authors.affiliation: Department of Oral and Craniofacial Biology, School of Dentistry, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Bitoun
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA Center for Oral Biology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Lemos
authors.affiliation: Department of Oral and Craniofacial Biology, School of Dentistry, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
authors.forename: Z T
authors.initials: ZT
authors.lastname: Wen
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA Center for Oral Biology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA Robert_Quivey@urmc.rochester.edu.
authors.forename: R G
authors.initials: RG
authors.lastname: Quivey
mesh_terms: D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects* / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000502:physiology; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D009243:NAD / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D013295:Streptococcus mutans / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
chemical_list: D009097:Multienzyme Complexes; D009243:NAD; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D010100:Oxygen