title: sigmaB regulates IS256-mediated Staphylococcus aureus biofilm phenotypic variation.
abstract: Biofilm formation in Staphylococcus aureus is subject to phase variation, and biofilm-negative derivatives emerge sporadically from a biofilm-positive bacterial population. To date, the only known mechanism for generating biofilm phenotypic variation in staphylococci is the reversible insertion/excision of IS256 in biofilm-essential genes. In this study, we present evidence suggesting that the absence of the sigma(B) transcription factor dramatically increases the rate of switching to the biofilm-negative phenotype in the clinical isolate S. aureus 15981, under both steady-state and flow conditions. The phenotypic switching correlates with a dramatic increase in the number of IS256 copies in the chromosomes of biofilm-negative variants, as well as with an augmented IS256 insertion frequency into the icaC and the sarA genes. IS256-mediated biofilm switching is reversible, and biofilm-positive variants could emerge from biofilm-negative sigma(B) mutants. Analysis of the chromosomal insertion frequency using a recombinant IS256 element tagged with an erythromycin marker showed an almost three-times-higher transposition frequency in a Deltasigma(B) strain. However, regulation of IS256 activity by sigma(B) appears to be indirect, since transposase transcription is not affected in the absence of sigma(B) and IS256 activity is inhibited to wild-type levels in a Deltasigma(B) strain under NaCl stress. Overall, our results identify a new role for sigma(B) as a negative regulator of insertion sequence transposition and support the idea that deregulation of IS256 activity abrogates biofilm formation capacity in S. aureus.
authors.affiliation: Instituto de Agrobiotecnología, Universidad Pública de Navarra, Pamplona-31006, Spain.
authors.forename: Jaione
authors.initials: J
authors.lastname: Valle
authors.forename: Marta
authors.initials: M
authors.lastname: Vergara-Irigaray
authors.forename: Nekane
authors.initials: N
authors.lastname: Merino
authors.forename: José R
authors.initials: JR
authors.lastname: Penadés
authors.forename: Iñigo
authors.initials: I
authors.lastname: Lasa
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D018441:Biofilms; D004251:DNA Transposable Elements; D014644:Genetic Variation; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012808:Sigma Factor / Q000235:genetics*; D013211:Staphylococcus aureus / Q000235:genetics / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D012808:Sigma Factor