Poster Presentation 12th Australian Peptide Conference 2017

Recombinant C-amidated antimicrobial peptide structural studies in whole bacteria using DNP solid-state NMR (#185)

Marc-Antoine Sani 1 , Daniel K Weber 1 , Sarah A Overall 1 , Frances Separovic 1
  1. University of Melbourne, Melbourne, VIC, Australia

Antimicrobial peptides (AMPs) have been extensively studied as promising alternatives to traditional antibiotics. Solid-state NMR has been used to characterise their effect on lipid bilayers, their primary target. Such studies are important to provide high-resolution details with a fully controlled and homogenous system, but correlation with in vivo remains speculative and highly dependent on choices of sample conditions (pH, temperature, lipid composition or peptide concentration). Studying AMPs in live bacteria is, therefore, attractive but challenged by the highly inhomogeneous and complicated architecture of bacteria coupled with strong background. To overcome the last point, we have designed a biosynthetic method to obtain the antimicrobial peptide maculatin 1.1 (Mac1) with good yield and possibility for C-amidation, allowing a series of isotopic enrichment schemes. Solid-state NMR allowed obtaining structural data on nucleic acids, lipids and peptides. 31P solid-state NMR showed the impact of Mac1 on live E. coli and S. aureus bacteria. Different levels of dynamic filtering coupled with paramagnetic reagents were used to isolate signals from different molecular species such as nucleic acids, lipids or inorganic phosphate. We also demonstrated the use of a spin-labelled Mac1 to enhance the signal of 15N and 13C labeled Mac1 peptides, which will allow peptide-peptide and peptide-bacteria interactions to be mapped.