title: Streptococcus mutans copper chaperone, CopZ, is critical for biofilm formation and competitiveness.
abstract: The oral cavity is a dynamic environment characterized by hundreds of bacterial species, saliva, and an influx of nutrients and metal ions such as copper. Although there is a physiologic level of copper in the saliva, the oral cavity is often challenged with an influx of copper ions. At high concentrations copper is toxic and must therefore be strictly regulated by pathogens for them to persist and cause disease. The cariogenic pathogen Streptococcus mutans manages excess copper using the copYAZ operon that encodes a negative DNA-binding repressor (CopY), the P1-ATPase copper exporter (CopA), and the copper chaperone (CopZ). These hypothetical roles of the copYAZ operon in regulation and copper transport to receptors led us to investigate their contribution to S. mutans virulence. Mutants defective in the copper chaperone CopZ, but not CopY or CopA, were impaired in biofilm formation and competitiveness against commensal streptococci. Characterization of the CopZ mutant biofilm revealed a decreased secretion of glucosyltransferases and reduced expression of mutacin genes. These data suggest that the function of copZ on biofilm and competitiveness is independent of copper resistance and CopZ is a global regulator for biofilm and other virulence factors. Further characterization of CopZ may lead to the identification of new biofilm pathways.
authors.affiliation: Department of Pediatric Dentistry, School of Dentistry, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Garcia
authors.affiliation: Department of Pediatric Dentistry, School of Dentistry, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Du
authors.affiliation: Department of Pediatric Dentistry, School of Dentistry, University of Alabama at Birmingham, Birmingham, AL, USA. hwu@uab.edu.
authors.forename: H
authors.initials: H
authors.lastname: Wu
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D018441:Biofilms / Q000254:growth & development*; D003300:Copper / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005964:Glucosyltransferases / Q000378:metabolism; D056265:Microbial Interactions; D018613:Microscopy, Confocal; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D009876:Operon; D060888:Real-Time Polymerase Chain Reaction; D013295:Streptococcus mutans / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D001426:Bacterial Proteins; C071263:CopA protein, Bacteria; D018832:Molecular Chaperones; D003300:Copper; D005964:Glucosyltransferases
keywords: 
  copYAZ
  ; dental caries; glucan matrix; mutacin