Nanoscale Forces at the Heart of Staphylococcus Infections

  • PDF / 2,124,372 Bytes
  • 6 Pages / 612 x 792 pts (letter) Page_size
  • 11 Downloads / 212 Views

DOWNLOAD

REPORT


1025-B04-10

Nanoscale Forces at the Heart of Staphylococcus Infections Ruchirej Yongsunthon1,2, Francis Paul Vellano2, Brian H. Lower3, Vance G. Fowler4, Emily Alexander4, and Steven K. Lower2 1 Corning Incorporated, Corning, NY, 14831 2 Ohio State University, Columbus, OH, 43210 3 Pacific Northwest National Laboratory, Richland, WA, 99352 4 Duke University, Durham, NC, 27710 ABSTRACT Staphylococcus aureus is one of the most frequently isolated bacteria from infected medical implants. S. aureus has the capacity to adhere to the surface of an implant where it forms a biofilm. We used atomic force microscopy to probe binding forces between a fibronectin-coated tip and isolates of S. aureus, which were obtained from either patients with infected prostheses or healthy humans. A unique force-signature was observed for binding events between the tip and the cells. There is a strong distinction (p=0.01) in the binding forcesignature observed for S. aureus isolated from the infected vs. healthy populations. This observation suggests a fundamental correlation between nanometer scale binding forces and the clinical outcome of patients with implanted medical devices. INTRODUCTION Surgical implants significantly improve the quality of life for many humans but also place these same patients at risk for life-threatening infections by bacteria (1). Staphylococcus aureus is the most frequently isolated microorganisms from such devices (1, 2). Mortality attributable to such S. aureus infections can be as high as 60% (3, 4). S. aureus colonize the surface of an implant by forming bonds with host ligands, such as fibronectin (Fn), which commonly coat a prosthetic device (5, 6). This type of bond is mediated by MSCRAMMs (microbial surface components that recognize adhesive matrix molecules) located on the cell wall of S. aureus (5, 7-12). A predominant MSCRAMM is fibronectin-binding protein (FnBP). We and others have used atomic force microscopy (AFM) or optical tweezers to probe the fundamental binding forces associated with type-strains or laboratory-derived strains of S. aureus (e.g., 13-16). These previous studies have been very useful, but they do not explore the binding mechanisms of the strains of S. aureus that actually cause complications in humans or “real world” clinical settings. All potentially devastating S. aureus biofilm infections have humble beginnings involving the attachment of a bacterium to a prosthetic device surface. To explore the figurative heart of Staphylococcus infections, it is necessary to investigate the fundamental forces of interaction which govern bacterial attachment. We have thus used AFM to measure binding forces between a simulated prosthetic device and several clinical isolates of S. aureus, which were obtained fromeither patients with an infected device or healthy subjects. These data suggest an intriguing correlation between the nanometer-scale forces at the bacterium-material interface and the clinical outcome of patients with implanted medical devices. An extended version of this study can b