Prevention of staphylococcal biofilm-associated infections by the quorum sensing inhibitor RIP.
Staphylococcus aureus and Staphylococcus epidermidis associated with implantable medical devices, are often difficult to treat with conventional antimicrobials. Formation of a biofilm and subsequent production of toxins are two distinct mechanisms considered important in foreign body infections. Staphylococcal virulence is caused by a complex regulatory process, which involves cell-to-cell communication through the release and response to chemical signals in a process known as quorum sensing. We explored the possibility of preventing infections by interfering with biofilm formation and toxin production using the quorum sensing inhibitor ribonucleic-acid-III-inhibiting peptide. In our studies ribonucleic-acid-III-inhibiting peptide prevented graft-associated infections caused by all species of staphylococci tested so far, including methicillin resistant S. aureus and S. epidermidis. Ribonucleic-acid-III-inhibiting peptide also enhances the effects of antibiotics and cationic peptides in the clearance of normally recalcitrant biofilm infections. Ribonucleic-acid-III-inhibiting peptide is nontoxic, highly stable, and no resistant strains have been found so far, suggesting that ribonucleic-acid-III-inhibiting peptide may be used to coat medical devices or used systemically to prevent infections. When the target of ribonucleic-acid-III activating protein activity is disrupted, biofilm formation is reduced under flow and static conditions and genes important for toxin production or biofilm formation are down-regulated. These in vitro data help explain why ribonucleic-acid-III-inhibiting peptide seems to be effective in preventing staphylococcal infections.
Balaban
Naomi
N
Tufts University School of Veterinary Medicine, Department of Biomedical Sciences, North Grafton, MA 01536, USA. naomi.balaban@tufts,edu
Stoodley
Paul
P
Fux
Christoph A
CA
Wilson
Suzanne
S
Costerton
J William
JW
Dell'Acqua
Giorgio
G
D000818:Animals; D001426:Bacterial Proteins / Q000187:drug effects / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D007274:Injections, Intraperitoneal; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D016459:Prosthesis-Related Infections / Q000382:microbiology / Q000517:prevention & control*; D016601:RNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013203:Staphylococcal Infections / Q000382:microbiology / Q000517:prevention & control*; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity*; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome; D014774:Virulence
D001426:Bacterial Proteins; C079092:MtrB protein, Bacteria; D009842:Oligopeptides; D016601:RNA-Binding Proteins; C111711:RNAIII inhibiting peptide; D014157:Transcription Factors