title: Beta toxin catalyzes formation of nucleoprotein matrix in staphylococcal biofilms.
abstract: Biofilms are surface-associated communities of microbes encompassed by an extracellular matrix. It is estimated that 80% of all bacterial infections involve biofilm formation, but the structure and regulation of biofilms are incompletely understood. Extracellular DNA (eDNA) is a major structural component in many biofilms of the pathogenic bacterium Staphylococcus aureus, but its role is enigmatic. Here, we demonstrate that beta toxin, a neutral sphingomyelinase and a virulence factor of S. aureus, forms covalent cross-links to itself in the presence of DNA (we refer to this as biofilm ligase activity, independent of sphingomyelinase activity) producing an insoluble nucleoprotein matrix in vitro. Furthermore, we show that beta toxin strongly stimulates biofilm formation in vivo as demonstrated by a role in causation of infectious endocarditis in a rabbit model. Together, these results suggest that beta toxin cross-linking in the presence of eDNA assists in forming the skeletal framework upon which staphylococcal biofilms are established.
authors.affiliation: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA. huse0050@umn.edu
authors.forename: Medora J
authors.initials: MJ
authors.lastname: Huseby
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Kruse
authors.forename: Jeff
authors.initials: J
authors.lastname: Digre
authors.forename: Petra L
authors.initials: PL
authors.lastname: Kohler
authors.forename: Jillian A
authors.initials: JA
authors.lastname: Vocke
authors.forename: Ethan E
authors.initials: EE
authors.lastname: Mann
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Bayles
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Bohach
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Schlievert
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Ohlendorf
authors.forename: Cathleen A
authors.initials: CA
authors.lastname: Earhart
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development*; D002384:Catalysis; D004269:DNA, Bacterial; D004696:Endocarditis; D006460:Hemolysin Proteins / Q000378:metabolism*; D009698:Nucleoproteins / Q000378:metabolism*; D011817:Rabbits; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*; D013210:Staphylococcus / Q000254:growth & development* / Q000472:pathogenicity
chemical_list: D001427:Bacterial Toxins; D004269:DNA, Bacterial; D006460:Hemolysin Proteins; D009698:Nucleoproteins; D013108:Sphingomyelin Phosphodiesterase; C029878:hlb protein, Staphylococcus aureus