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Antimicrobial Agents and Chemotherapy, November 2003, p. 3407-3414, Vol. 47, No. 11
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.11.3407-3414.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Lysostaphin Disrupts Staphylococcus aureus and Staphylococcus epidermidis Biofilms on Artificial Surfaces

Julie A. Wu,{dagger} Caroline Kusuma, James J. Mond, and John F. Kokai-Kun*

Biosynexus Incorporated, Gaithersburg, Maryland

Received 6 January 2003/ Returned for modification 9 June 2003/ Accepted 16 July 2003

Staphylococci often form biofilms, sessile communities of microcolonies encased in an extracellular matrix that adhere to biomedical implants or damaged tissue. Infections associated with biofilms are difficult to treat, and it is estimated that sessile bacteria in biofilms are 1,000 to 1,500 times more resistant to antibiotics than their planktonic counterparts. This antibiotic resistance of biofilms often leads to the failure of conventional antibiotic therapy and necessitates the removal of infected devices. Lysostaphin is a glycylglycine endopeptidase which specifically cleaves the pentaglycine cross bridges found in the staphylococcal peptidoglycan. Lysostaphin kills Staphylococcus aureus within minutes (MIC at which 90% of the strains are inhibited [MIC90], 0.001 to 0.064 µg/ml) and is also effective against Staphylococcus epidermidis at higher concentrations (MIC90, 12.5 to 64 µg/ml). The activity of lysostaphin against staphylococci present in biofilms compared to those of other antibiotics was, however, never explored. Surprisingly, lysostaphin not only killed S. aureus in biofilms but also disrupted the extracellular matrix of S. aureus biofilms in vitro on plastic and glass surfaces at concentrations as low as 1 µg/ml. Scanning electron microscopy confirmed that lysostaphin eradicated both the sessile cells and the extracellular matrix of the biofilm. This disruption of S. aureus biofilms was specific for lysostaphin-sensitive S. aureus, as biofilms of lysostaphin-resistant S. aureus were not affected. High concentrations of oxacillin (400 µg/ml), vancomycin (800 µg/ml), and clindamycin (800 µg/ml) had no effect on the established S. aureus biofilms in this system, even after 24 h. Higher concentrations of lysostaphin also disrupted S. epidermidis biofilms.

* Corresponding author. Mailing address: Biosynexus Incorporated, 9119 Gaither Rd., Gaithersburg, MD 20877. Phone: (301) 987-1172. Fax: (301) 990-4990. E-mail: johnkun{at}biosynexus.com.

{dagger} Present address: Department of Molecular and Cell Biology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.

Antimicrobial Agents and Chemotherapy, November 2003, p. 3407-3414, Vol. 47, No. 11
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.11.3407-3414.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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