Poster Presentation International Peptide Symposium 2023

Discovering Novel Natural Products to Combat Antibiotic Resistant Pathogens (#322)

Negero Negeri 1 2 , Sacha Pidot 1 3 , Jennifer Payne 1 2 , Chuan Huang 1 2 , Max Cryle 1 2
  1. Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, Melbourne, Victoria, Australia
  2. Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
  3. Department of Microbiology and Immunology, University of Melbourne, Melbourne, victoria, Australia

As the pressure from antimicrobial resistance is mounting, seriously threatening our ability to control the infection, it is vitally important to stress the ongoing search to supply new antibiotics, particularly by expanding the search towards understudied sources . Soil bacteria have been an excellent source of antibiotics; however, standard cultivation techniques are only capable of cultivating less than 1% of these. Here we have used IChip technology to isolate and screen antimicrobial producing bacteria from Australian soils. We recovered 141 bacterial isolates and screened these for antimicrobial activity against multidrug-resistant clinical pathogens. We found 48% of isolates inhibited at least one organism in our test panel. Using high-resolution mass spectrometry (HRMS) we have identified metabolites from our bacterial culture extracts. We have dereplicated known antibiotics produced by our isolates by comparison of MS/MS fragmentation data to the GNPS database and annotation with Dereplecator +. Whilst we have detected several known bioactive compounds in these crude extracts, the majority of the isolates show no hits to the known antimicrobial compounds, highlighting the potential of those isolates to biosynthesise new compounds. The analysis of the Genome of selected 8 bioactive iChip-derived isolates using antiSMASH and PRISM have identified 244 BGCs encoding secondary metabolites. Further characterization of these BGC and linking genomic information with metabolites detected in the MS spectrometer is underway, which will help us select promising BGCs for cloning and heterologous expression. In conclusion, this study highlights that Australian soil bacteria represent an untapped resource for the discovery of potentially new bioactive molecules.