A worldwide public health problem has resulted from the alarming spread of multi-drug resistant bacteria combined
with the frequent occurrence of biofilm-type infections, creating a growing need for new therapies. In this study, we
have demonstrated that novel cyclic lipopeptides, such as 1, cyclo-[D-Ala-(12-guanidinododecanoyl)Thr-D-Val-Val-DaThr-D-Asn], and 2, cyclo-[D-Ala-(12-guanidinododecanoyl)Dap-D-Val-Val-D-aThr-D-Asn], derived from the fusaricidin/
LI-F natural products efficiently inhibit the growth of Staphylococcus aureus biofilm in vitro at their minimum inhibitory
concentrations (MICs). Complete S. aureus biofilm eradication was observed at 3 x MIC for 1 and 4 x MIC for 2.
Promising in vivo activity was demonstrated by the ability of depsipeptide 1 to reduce the proliferation of methicillinresistant
S. aureus US300 in a porcine wound model. Due to their unique structure and potent antibacterial and antibiofilm
activities, cyclic lipopeptides that belong to the fusaricidin/LI-F family of antibiotics represent particularly attractive lead
structures for the development of new antibacterial agents capable of treating complicated biofilm-associated infections.
Keywords: Antibiotics, biofilm, cyclic lipopeptides, eradication, fusaricidins/LI-Fs, MRSA, porcine model, wound.
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