Affiliation:
1. Biosynexus Incorporated, Gaithersburg, Maryland
Abstract
ABSTRACT
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 [MIC
90
], 0.001 to 0.064 μg/ml) and is also effective against
Staphylococcus epidermidis
at higher concentrations (MIC
90
, 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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference42 articles.
1. Amorena, B., E. Gracia, M. Monzón, J. Leiva, C. Oteiza, M. Pérez, J. Alabart, and J. Hernández-Yago. 1999. Antibiotic susceptibility assay for Staphylococcus aureus in biofilms developed in vitro. J. Antimicrob. Chemother.44:43-55.
2. Bellón, J. M., N. G-Honduvilla, F. Jurado, A. G-Carranza, and J. Buján. 2001. In vitro interaction of bacteria with polypropylene/ePTFE prostheses. Biomaterials22:2021-2024.
3. Browder, H., W. Zygmunt, J. Young, and P. Travormina. 1965. Lysostaphin: enzymatic mode of action. Biochem. Biophys. Res. Commun.19:383-389.
4. Centers for Disease Control and Prevention. 1998. Preventing emerging infectious diseases: a strategy for the 21st century. Centers for Disease Control and Prevention Atlanta Ga.
5. Chamis, A., G. Peterson, C. Cabell, G. Corey, G. Sorrentino, R. Greenfield, R. Thomas, L. Reller, and V. Fowler. 2001. Staphylococcus aureus bacteremia in patients with permanent pacemakers or implantable cardioverter-defibrillators. Circulation104:1029-1033.
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