The staphylococci are the leading cause of infections related to implantable medical devices. Biofilm production is an important aspect of the pathogenesis of such infections. The polysaccharide beta-1,6- linked N-acetylglucosamine (PNAG) is critical to biofilm elaboration in both Staphylococcus aureus and co-agulase-negative staphylococci (ConNS) and is synthesized from proteins encoded in the intercellular adhesion (ica) locus. The goal of this study is to characterize the mechanism through which the ica locus is regulated in S. aureus. Whereas S. epidermidis elaborates biofilm constitutively, S. aureus does not produce PNAG under typical in vitro conditions but requires a stimulus, such as iron deprivation or >0.5% glucose. A clinical isolate of S. aureus, MN8, underwent a spontaneous mutation resulting in constitutive over-production of PNAG. In the first part of this study, the DNA sequence of the ica locus from the PNAG-constitutive strain (MN8m) will be compared with that of PNAG-inducible strains of S. aureus and the ability of MN8m ica will e assessed by Northern analysis and via DNA affinity of ica promoter-binding proteins. Finally, virulence of MN8m will be compared with that of PNAG-inducible strains of S. aureus in the mouse model of renal infection.
| Jefferson, Kimberly K; Goldmann, Donald A; Pier, Gerald B (2005) Use of confocal microscopy to analyze the rate of vancomycin penetration through Staphylococcus aureus biofilms. Antimicrob Agents Chemother 49:2467-73 |
| Jefferson, Kimberly K; Pier, Danielle B; Goldmann, Donald A et al. (2004) The teicoplanin-associated locus regulator (TcaR) and the intercellular adhesin locus regulator (IcaR) are transcriptional inhibitors of the ica locus in Staphylococcus aureus. J Bacteriol 186:2449-56 |
| Jefferson, Kimberly K; Cramton, Sarah E; Gotz, Friedrich et al. (2003) Identification of a 5-nucleotide sequence that controls expression of the ica locus in Staphylococcus aureus and characterization of the DNA-binding properties of IcaR. Mol Microbiol 48:889-99 |
