title: Deficiency of PdxR in Streptococcus mutans affects vitamin B6 metabolism, acid tolerance response and biofilm formation.
abstract: Streptococcus mutans, a key etiological agent of the human dental caries, lives primarily on the tooth surface in tenacious biofilms. The SMU864 locus, designated pdxR, is predicted to encode a member of the novel MocR/GabR family proteins, which are featured with a winged helix DNA-binding N-terminal domain and a C-terminal domain highly homologous to the pyridoxal phosphate-dependent aspartate aminotransferases. A pdxR-deficient mutant, TW296, was constructed using allelic exchange. PdxR deficiency in S. mutans had little effect on cell morphology and growth when grown in brain heart infusion. However, when compared with its parent strain, UA159, the PdxR-deficient mutant displayed major defects in acid tolerance response and formed significantly fewer biofilms (P < 0.01). When analyzed by real-time polymerase chain reaction, PdxR deficiency was found to drastically reduce expression of an apparent operon encoding a pyridoxal kinase (SMU865) and a pyridoxal permease (SMU866) of the salvage pathway of vitamin B6 biosynthesis. In addition, PdxR deficiency also altered the expression of genes for ClpL protease, glucosyltransferase B and adhesin SpaP, which are known to play important roles in stress tolerance and biofilm formation. Consistently, PdxR-deficiency affected the growth of the deficient mutant when grown in defined medium with and without vitamin B6 . Further studies revealed that although S. mutans is known to require vitamin B6 to grow in defined medium, B6 vitamers, especially pyridoxal, were strongly inhibitory at millimolar concentrations, against S. mutans growth and biofilm formation. Our results suggest that PdxR in S. mutans plays an important role in regulation of vitamin B6 metabolism, acid tolerance response and biofilm formation.
authors.affiliation: Department of Oral and Craniofacial Biology, Louisiana State University Health Sciences Center, New Orleans, LA, USA.|Department of Comprehensive Dentistry and Biomaterials, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Liao
authors.affiliation: Department of Oral and Craniofacial Biology, Louisiana State University Health Sciences Center, New Orleans, LA, USA.|Department of Comprehensive Dentistry and Biomaterials, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors.forename: J P
authors.identifier: http://orcid.org/0000-0001-7110-2328
authors.initials: JP
authors.lastname: Bitoun
authors.affiliation: Department of Oral and Craniofacial Biology, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Nguyen
authors.affiliation: Center of Excellence for Oral and Craniofacial Biology, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Bozner
authors.affiliation: Department of Oral and Craniofacial Biology, Louisiana State University Health Sciences Center, New Orleans, LA, USA.|Department of Comprehensive Dentistry and Biomaterials, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors.forename: X
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Oral and Craniofacial Biology, Louisiana State University Health Sciences Center, New Orleans, LA, USA.|Department of Comprehensive Dentistry and Biomaterials, Louisiana State University Health Sciences Center, New Orleans, LA, USA.|Center of Excellence for Oral and Craniofacial Biology, Louisiana State University Health Sciences Center, New Orleans, LA, USA.|Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors.forename: Z T
authors.initials: ZT
authors.lastname: Wen
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics; D000596:Amino Acids / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D003470:Culture Media / Q000737:chemistry; D015964:Gene Expression Regulation, Bacterial; D005964:Glucosyltransferases / Q000235:genetics; D006801:Humans; D009154:Mutation; D009876:Operon; D011730:Pyridoxal / Q000494:pharmacology; D011731:Pyridoxal Kinase / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013295:Streptococcus mutans / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics; D000637:Transaminases / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D025101:Vitamin B 6 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D000596:Amino Acids; D001426:Bacterial Proteins; D003470:Culture Media; D014157:Transcription Factors; D011730:Pyridoxal; D025101:Vitamin B 6; C036655:1,3-alpha-D-glucan synthase; D005964:Glucosyltransferases; D000637:Transaminases; D011731:Pyridoxal Kinase
keywords: MocR/GabR family proteins; Streptococcus mutans; dental caries; vitamin B6