Beta toxin catalyzes formation of nucleoprotein matrix in staphylococcal biofilms.
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.
Huseby
Medora J
MJ
Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA. huse0050@umn.edu
Kruse
Andrew C
AC
Digre
Jeff
J
Kohler
Petra L
PL
Vocke
Jillian A
JA
Mann
Ethan E
EE
Bayles
Kenneth W
KW
Bohach
Gregory A
GA
Schlievert
Patrick M
PM
Ohlendorf
Douglas H
DH
Earhart
Cathleen A
CA
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
D001427:Bacterial Toxins; D004269:DNA, Bacterial; D006460:Hemolysin Proteins; D009698:Nucleoproteins; D013108:Sphingomyelin Phosphodiesterase; C029878:hlb protein, Staphylococcus aureus