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Infection and Immunity, August 2005, p. 4596-4606, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4596-4606.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Heparin Stimulates Staphylococcus aureus Biofilm Formation

Robert M. Q. Shanks,1 Niles P. Donegan,1 Martha L. Graber,2 Sarah E. Buckingham,1 Michael E. Zegans,1,3 Ambrose L. Cheung,1 and George A. O'Toole1*

Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, New Hampshire 03755,1 Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire 03766,2 Department of Surgery, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire 037663

Received 12 January 2005/ Returned for modification 11 February 2005/ Accepted 17 March 2005

Heparin, known for its anticoagulant activity, is commonly used in catheter locks. Staphylococcus aureus, a versatile human and animal pathogen, is commonly associated with catheter-related bloodstream infections and has evolved a number of mechanisms through which it adheres to biotic and abiotic surfaces. We demonstrate that heparin increased biofilm formation by several S. aureus strains. Surface coverage and the kinetics of biofilm formation were stimulated, but primary attachment to the surface was not affected. Heparin increased S. aureus cell-cell interactions in a protein synthesis-dependent manner. The addition of heparin rescued biofilm formation of hla, ica, and sarA mutants. Our data further suggest that heparin stimulation of biofilm formation occurs neither through an increase in sigB activity nor through an increase in polysaccharide intracellular adhesin levels. These finding suggests that heparin stimulates S. aureus biofilm formation via a novel pathway.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, New Hampshire 03755. Phone: 603-650-1248. Fax: 603-650-1245. E-mail: georgeo{at}dartmouth.edu.

Editor: J. T. Barbieri

Infection and Immunity, August 2005, p. 4596-4606, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4596-4606.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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