title: In vitro and in vivo activities of novel cyclic lipopeptides against staphylococcal biofilms.
abstract: 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.
authors.forename: Nina
authors.initials: N
authors.lastname: Bionda
authors.forename: Irena
authors.initials: I
authors.lastname: Pastar
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Davis
authors.affiliation: Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, Florida 34987 (USA). pcudic@tpims.org.
authors.forename: Predrag
authors.initials: P
authors.lastname: Cudic
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D055666:Lipopeptides / Q000737:chemistry* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000502:physiology*; D013552:Swine; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D055666:Lipopeptides; D010456:Peptides, Cyclic