TY - JOUR
T1 - RNAIII-inhibiting peptide improves efficacy of clinically used antibiotics in a murine model of staphylococcal sepsis
AU - Giacometti, Andrea
AU - Cirioni, Oscar
AU - Ghiselli, Roberto
AU - Dell'Acqua, Giorgio
AU - Orlando, Fiorenza
AU - D'Amato, Giuseppina
AU - Mocchegiani, Federico
AU - Silvestri, Carmela
AU - Prete, Maria Simona Del
AU - Rocchi, Marco
AU - Balaban, Naomi
AU - Saba, Vittorio
AU - Scalise, Giorgio
PY - 2005/2
Y1 - 2005/2
N2 - RNAIII-inhibiting peptide (RIP, YSPWTNF-NH 2) 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 × 10 6 CFU of S. aureus ATCC 25923 or with 3.0 × 10 6 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 (2 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.
AB - RNAIII-inhibiting peptide (RIP, YSPWTNF-NH 2) 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 × 10 6 CFU of S. aureus ATCC 25923 or with 3.0 × 10 6 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 (2 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.
KW - Bacteremia
KW - Exotoxins
KW - RNAIII-inhibiting peptide
KW - Staphylococcus aureus
KW - Vancomycin
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U2 - 10.1016/j.peptides.2004.09.018
DO - 10.1016/j.peptides.2004.09.018
M3 - Article
C2 - 15629527
AN - SCOPUS:19944372026
VL - 26
SP - 169
EP - 175
JO - Peptides
JF - Peptides
SN - 0196-9781
IS - 2
ER -