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Infectious disease


Bacterial lipid II

In silico, in vitro and mouse studies suggest a compound that mimics the antimicrobial peptide defensin a1 (DEFA1; HNP-1) could be used to treat sepsis. In silico, SAR and biological analyses identified low-molecular weight compounds that mimicked the structure of DEFA1 bound to lipid II, a bacterial cell wall precursor. In antibacterial assays, the lead compound killed Gram-positive bacterial isolates as well as Escherichia coli by inhibiting cell wall synthesis. In a mouse model of Staphylococcus aureus-induced sepsis, the lead compound prevented the deaths of four out of five mice, whereas vancomycin prevented the death of five out of five mice and vehicle did not prevent death. Next steps include SAR studies and optimization of the lead compound.
Cellceutix Corp.'s brilacidin, a synthetic defensin mimetic, has completed Phase II trials to treat acute bacterial skin and skin structure infection (ABSSSI).

SciBX 7(1); doi:10.1038/scibx.2014.23
Published online Jan. 9, 2014

Patent application filed; available for licensing from the University of Maryland, Baltimore Office of Research and Development

Varney, K.M. et al. PLoS Pathog.; published online Nov. 7, 2013;
Contact: Erik P.H. de Leeuw, University of Maryland School of Medicine, Baltimore, Md.