title: Inactivation of the spxA1 or spxA2 gene of Streptococcus mutans decreases virulence in the rat caries model.
abstract: In oral biofilms, the major environmental challenges encountered by Streptococcus mutans are acid and oxidative stresses. Previously, we showed that the transcriptional regulators SpxA1 and SpxA2 are involved in general stress survival of S. mutans with SpxA1 playing a primary role in activation of antioxidant and detoxification strategies whereas SpxA2 serves as a back up activator of oxidative stress genes. We have also found that spxA1 mutant strains (∆spxA1 and ∆spxA1∆spxA2) are outcompeted by peroxigenic oral streptococci in vitro and have impaired abilities to colonize the teeth of rats fed a highly cariogenic diet. Here, we show that the Spx proteins can also exert regulatory roles in the expression of additional virulence attributes of S. mutans. Competence activation is significantly impaired in Δspx strains and the production of mutacin IV and V is virtually abolished in ΔspxA1 strains. Unexpectedly, the ∆spxA2 strain showed increased production of glucans from sucrose, without affecting the total amount of bacteria within biofilms when compared with the parent strain. By using the rat caries model, we showed that the capacity of the ΔspxA1 and ΔspxA2 strains to cause caries on smooth tooth surfaces is significantly impaired. The ∆spxA2 strain also formed fewer lesions on sulcal surfaces. This report reveals that global regulation via Spx contributes to the cariogenic potential of S. mutans and highlights that animal models are essential in the characterization of bacterial traits implicated in virulence.
authors.affiliation: Center for Oral Biology and Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA.|Department of Physiological Sciences, Dentistry School of Piracicaba, State University of Campinas, Piracicaba, SP, Brazil.
authors.forename: L C C
authors.initials: LC
authors.lastname: Galvão
authors.affiliation: Department of Physiological Sciences, Dentistry School of Piracicaba, State University of Campinas, Piracicaba, SP, Brazil.
authors.forename: P L
authors.initials: PL
authors.lastname: Rosalen
authors.affiliation: Center for Oral Biology and Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: I
authors.initials: I
authors.lastname: Rivera-Ramos
authors.affiliation: Department of Physiological Sciences, Dentistry School of Piracicaba, State University of Campinas, Piracicaba, SP, Brazil.|Department of General Biology, Laboratory of Physiology and Pathophysiology, State University of Ponta Grossa, Ponta Grossa, PR, Brazil.
authors.forename: G C N
authors.initials: GC
authors.lastname: Franco
authors.affiliation: Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Kajfasz
authors.affiliation: Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL, USA.
authors.forename: J
authors.initials: J
authors.lastname: Abranches
authors.affiliation: Department of Physiological Sciences, Dentistry School of Piracicaba, State University of Campinas, Piracicaba, SP, Brazil.|Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: B
authors.initials: B
authors.lastname: Bueno-Silva
authors.affiliation: Biofilm Research Laboratory, Department of Orthodontics and Divisions of Pediatric Dentistry & Community Oral Health, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Koo
authors.affiliation: Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Lemos
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D001430:Bacteriocins / Q000494:pharmacology; D018441:Biofilms; D003731:Dental Caries / Q000382:microbiology*; D004195:Disease Models, Animal; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D020868:Gene Silencing; D009154:Mutation; D018384:Oxidative Stress / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013295:Streptococcus mutans / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D014157:Transcription Factors / Q000235:genetics*; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D001430:Bacteriocins; D014157:Transcription Factors; C425769:mutacin IV
keywords: 
  Streptococcus mutans
  ; Spx; dental caries; oxidative stress