Poster Presentation 13th Australian Peptide Conference 2019

Enhancing activity by combining antimicrobial peptides and antibiotics (#204)

Dean Sheard 1 , Neil O'Brien-Simpson 2 , Frances Separovic 1 , John Wade 3
  1. School of Chemistry, Bio21 Institute, University of Melbourne, Melbourne, Victoria, Australia
  2. Melbourne Dental School, Centre for Oral Health Research, University of Melbourne, Melbourne, Victoria, Australia
  3. Howard Florey Research Laboratories, Florey Institute for Neuroscience & Mental Health, University of Melbourne, Melbourne, Victoria, Australia

Bacterial resistance has become a global issue due to the inappropriate use of antibiotics and the rise of multidrug resistant (MDR) bacteria. Novel strategies are needed to stem this spread of resistance and combining antimicrobial peptides (AMPs) with antibiotics has shown promising synergistic effects. Combination therapy has been often used to combat resistance and the combination of AMPs with antibiotics is a logical development. The covalent linkage of these molecules may create compounds with greater activity and reduced toxicity and confound the resistance mechanisms of MDR bacteria. This could lead to previously ineffective antibiotics once again to become effective against the MDR strains. We aim to produce synergistic effects by using several proline-rich AMPs and a range of antibiotic types. The AMP, Chex1-Arg20, is the monomeric form of the designed A3-APO cell penetrating peptide and has shown activity against resistant bacterial strains. The antimicrobial activity of several peptides based on the Chex1-Arg20 sequence have been tested in combination with aminoglycoside antibiotics, such as Kanamycin. Those combinations that exhibit synergistic activity will inform us which are the best candidates to link covalently for further studies.