In vitro and in vivo activities of novel cyclic lipopeptides against staphylococcal biofilms

Nina Bionda, Irena Pastar, Stephen C. Davis, Predrag Cudic

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)352-356
Number of pages5
JournalProtein and Peptide Letters
Volume21
Issue number4
DOIs
StatePublished - Apr 2014

Keywords

  • Antibiotics
  • Biofilm
  • Cyclic lipopeptides
  • Eradication
  • Fusaricidins/LI-Fs
  • MRSA
  • Porcine model
  • Wound

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology

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