posters 5th Asia-Pacific NMR Symposium 2013

Antimicrobial peptide – structure, function and serine protease inhibitors (#175)

Uru Malik 1 , Osmar N Silva 2 , Isabel CM Fensterseifer 2 , Richard J Clark 3 , Phillip S Walsh 1 , Philip E Sunderland 1 , Octavio L Franco 2 , Norelle L Daly 4 , David J Craik 1
  1. Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
  2. Centro de Análises Proteômicas e Bioquímicas, Universidade Católica de Brasília, Brasília, Brazil
  3. School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia
  4. Centre for Biodiscovery and Molecular Development of Therapeutics, James Cook University, Cairns, QLD, Australia

Staphylococcus aureus is one of the most notorious and virulent pathogens and its resistance against existing antimicrobial drugs is a global concern. Highly resistant bacterial strains such as methicillin-resistant Staphylococcus aureus cause approximately 60% of hospital acquired infections1. Antimicrobial peptides (AMPs) could be a potential solution to this problem, as resistance against them is thought to be improbable as they target microbial membranes2. In the current study we have examined the antimicrobial properties of peptides isolated from frog skin secretions using in vivo and in vitro antibacterial assays. Several peptides showed potent antibacterial activity against Staphylococcus aureus, which was comparable to neomycin, and the peptides were not hemolytic up to 50 mM. Highly active peptides were successfully cyclized by native chemical ligation and they maintained the biological activity and structural characteristics of the linear form. The structure of the peptides elucidated by NMR spectroscopy revealed high structural similarity to SFTI-1, a cyclic peptide discovered from sunflower, along with sequence similarity. Structure-function relationship provided insights towards the development of bi-functional peptides with both potent in vivo antimicrobial activity and serine protease inhibitory activity. AMPs are one of the most promising therapeutic strategies for combating infections and this work could offer therapeutic solutions against clinically resistant microbes3,4.


1 S.K. Fridkin: New England Journal of Medicine, 2005, 352, 1436-1444

2 M. Zasloff: Nature 2002, 415, 389-395.

3 R.E.W. Hancock, D.S. Chapple: Antimicrobial Agents and Chemotherapy, 1999, 43, 1317-1323.

4 World Health Organization (WHO): World Health Day - 2011