Comparative impact of diverse regulatory loci on Staphylococcus aureus biofilm formation

Microbiologyopen. 2015 Jun;4(3):436-51. doi: 10.1002/mbo3.250. Epub 2015 Mar 21.


The relative impact of 23 mutations on biofilm formation was evaluated in the USA300, methicillin-resistant strain LAC. Mutation of sarA, atl, codY, rsbU, and sigB limited biofilm formation in comparison to the parent strain, but the limitation imposed by mutation of sarA was greater than that imposed by mutation of any of these other genes. The reduced biofilm formation of all mutants other than the atl mutant was correlated with increased levels of extracellular proteases. Mutation of fur- and mgrA-enhanced biofilm formation but in LAC had no impact on protease activity, nuclease activity, or accumulation of the polysaccharide intercellular adhesin (PIA). The increased capacity of these mutants to form a biofilm was reversed by mutation of sarA, and this was correlated with increased protease production. Mutation of sarA, mgrA, and sigB had the same phenotypic effect in the methicillin-sensitive strain UAMS-1, but mutation of codY increased rather than decreased biofilm formation. As with the UAMS-1 mgrA mutant, this was correlated with increased production of PIA. Examination of four additional clinical isolates suggests that the differential impact of codY on biofilm formation may be a conserved characteristic of methicillin-resistant versus methicillin-sensitive strains.

Keywords: Biofilm; Staphylococcus aureus; protease; regulation; sarA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biofilms*
  • Deoxyribonucleases / metabolism
  • Extracellular Space / metabolism
  • Gene Expression Regulation, Bacterial*
  • Genetic Loci*
  • Mutation
  • Peptide Hydrolases / biosynthesis
  • Phenotype
  • Regulatory Sequences, Nucleic Acid
  • Staphylococcus aureus / genetics*
  • Staphylococcus aureus / growth & development*
  • Staphylococcus aureus / metabolism


  • Deoxyribonucleases
  • Peptide Hydrolases