TY - JOUR
T1 - A chimeric peptide composed of a dermaseptin derivative and an RNA III-inhibiting peptide prevents graft-associated infections by antibiotic-resistant staphylococci
AU - Balaban, Naomi
AU - Gov, Yael
AU - Giacometti, Andrea
AU - Cirioni, Oscar
AU - Ghiselli, Roberto
AU - Mocchegiani, Federico
AU - Orlando, Fiorenza
AU - D'Amato, Giuseppina
AU - Saba, Vittorio
AU - Scalise, Giorgio
AU - Bernes, Sabina
AU - Mor, Amram
PY - 2004/7
Y1 - 2004/7
N2 - Staphylococcal bacteria are a prevalent cause of infections associated with foreign bodies and indwelling medical devices. Bacteria are capable of escaping antibiotic treatment through encapsulation into biofilms. RNA III-inhibiting peptide (RIP) is a heptapeptide that inhibits staphylococcal biofilm formation by obstructing quorum-sensing mechanisms. K4-S4(1-13)a is a 13-residue dermaseptin derivative (DD13) believed to kill bacteria via membrane disruption. We tested each of these peptides as well as a hybrid construct, DD13-RIP, for their ability to inhibit bacterial proliferation and suppress quorum sensing in vitro and for their efficacy in preventing staphylococcal infection in a rat graft infection model with methicillin-resistant Staphylococcus aureus (MRSA) or S. epidermidis (MRSE). In vitro, proliferation assays demonstrated that RIP had no inhibitory effect, while DD13-RIP and DD13 were equally effective, and that the chimeric peptide but not DD13 was slightly more effective than RIP in inhibiting RNA III synthesis, a regulatory RNA molecule important for staphylococcal pathogenesis. In vivo, the three peptides reduced graft-associated bacterial load in a dose-dependent manner, but the hybrid peptide was most potent in totally preventing staphylococcal infections at the lowest dose. In addition, each of the peptides acted synergistically with antibiotics. The data indicate that RIP and DD13 act in synergy by attacking bacteria simultaneously by two different mechanisms. Such a chimeric peptide may be useful for coating medical devices to prevent drug-resistant staphylococcal infections.
AB - Staphylococcal bacteria are a prevalent cause of infections associated with foreign bodies and indwelling medical devices. Bacteria are capable of escaping antibiotic treatment through encapsulation into biofilms. RNA III-inhibiting peptide (RIP) is a heptapeptide that inhibits staphylococcal biofilm formation by obstructing quorum-sensing mechanisms. K4-S4(1-13)a is a 13-residue dermaseptin derivative (DD13) believed to kill bacteria via membrane disruption. We tested each of these peptides as well as a hybrid construct, DD13-RIP, for their ability to inhibit bacterial proliferation and suppress quorum sensing in vitro and for their efficacy in preventing staphylococcal infection in a rat graft infection model with methicillin-resistant Staphylococcus aureus (MRSA) or S. epidermidis (MRSE). In vitro, proliferation assays demonstrated that RIP had no inhibitory effect, while DD13-RIP and DD13 were equally effective, and that the chimeric peptide but not DD13 was slightly more effective than RIP in inhibiting RNA III synthesis, a regulatory RNA molecule important for staphylococcal pathogenesis. In vivo, the three peptides reduced graft-associated bacterial load in a dose-dependent manner, but the hybrid peptide was most potent in totally preventing staphylococcal infections at the lowest dose. In addition, each of the peptides acted synergistically with antibiotics. The data indicate that RIP and DD13 act in synergy by attacking bacteria simultaneously by two different mechanisms. Such a chimeric peptide may be useful for coating medical devices to prevent drug-resistant staphylococcal infections.
UR - http://www.scopus.com/inward/record.url?scp=3042533905&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=3042533905&partnerID=8YFLogxK
U2 - 10.1128/AAC.48.7.2544-2550.2004
DO - 10.1128/AAC.48.7.2544-2550.2004
M3 - Article
C2 - 15215107
AN - SCOPUS:3042533905
VL - 48
SP - 2544
EP - 2550
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 7
ER -