Abstract

RNAIII-inhibiting peptide (RIP, YSPWTNF-NH₂) is a quorum-sensing peptide inhibitor that prevents Staphylococcus aureus toxin production and biofilm formation. A mouse sepsis model was used to test the efficacy of RIP alone or in combination with conventional antibiotics in suppressing S. aureus-induced sepsis. Mice were injected intravenously with 3.0 × 10⁶ CFU of S. aureus ATCC 25923 or with 3.0 × 10⁶ CFU of S. aureus strain Smith diffuse. All animals were randomized to receive intravenously isotonic sodium chloride solution as a control, or 20 mg/kg RIP alone or combined with 20 mg/kg cefazolin, 10 mg/kg imipenem, or 10 mg/kg vancomycin immediately or 6 h after bacterial challenge. Main outcome measures were bacteremia and lethality. All compounds reduced lethality when compared to controls. Although, in general combined-treated groups had significant lower bacterial counts when associated to singly-treated groups only the combination between RIP and vancomycin with respect to cefazolin gave a statistically significant decrease in the lethality rate. Lowest lethality rates (10%) and bacteremia (<10² CFU/ml) were obtained when RIP was administered in combination with vancomycin. Because RIP can be synergistic with current antibiotic therapies and help to reduce S. aureus exotoxins production, it can be considered a promising agent to associate with antibiotics for further clinical research into treatment of sepsis.

Keywords: Vancomycin; Staphylococcus aureus; RNAIII-inhibiting peptide; Bacteremia; Exotoxins

Article Outline

1. Introduction

2. Materials and methods

2.1. Organisms

2.2. Drugs

2.3. Susceptibility testing

2.4. Animals

2.5. Preparation of inoculum S. aureus

2.6. Bacterial challenge

2.7. Antibiotic therapy

2.8. Evaluation of treatment

2.9. Statistical analysis

3. Results

3.1. Susceptibility testing

3.2. In vivo studies

4. Discussion

Acknowledgements

References