Pidot Laboratory: Antibiotic Discovery and Biosynthesis

The Pidot Laboratory uses a combination of microbiology, genomics and biological chemistry to identify new antimicrobials and investigate their biosynthesis. We then try to translate this knowledge into new medicines that will benefit humans. We have a particular focus on unusual actinomycetes, especially those that cause infections in humans and animals. We use a variety of state-of-the-art techniques ranging from bioinformatics and molecular microbiology to isolation chemistry and mass spectrometry to uncover and investigate bacterial metabolites that kill other bacteria.

Specific areas are outlined below:

• Identification of new antimicrobials.
  Despite their ability to cause disease, bacteria are also a major source of drugs that are currently used to treat microbial infections. These compounds sourced from nature are known as natural products. Our research seeks to identify these pharmacologically useful molecules and to investigate their microbial biosynthesis. Our main priority is to identify and produce new antibiotics and we aim to achieve this through a combination of genomic, microbiological and chemical methods. These methods also allow us to investigate the biosynthetic pathways through which these molecules are produced. Techniques involved in our studies include: DNA sequencing and bioinformatic analysis; antimicrobial assays DNA manipulation and genetic exchange; natural product isolation and structure elucidation; and illuminating microbial "dark matter". While the rediscovery of known compounds is a significant problem when empirically screening bacteria for antibiotic production, multiple genomics studies have shown that the well of antimicrobials is not yet dry and there are many more potential compounds to find. However, the majority of these identified biosynthetic loci appear to be silent under standard culture conditions. We use a combination of approaches (genetic, biochemical and microbiological) to activate these cryptic gene clusters and identify the resulting metabolites.
• Culturing the "unculturable".
  The vast majority of bioactive natural products have been identified from soil bacteria. Yet, it is estimated that we have only been able to culture between 0.1-1% of the bacteria present in soil. By gaining access to previously uncultured microbes, we have the potential to identify previously unseen antimicrobials. We use a combination of innovative culture techniques to grow bacteria hiding within soil and to investigate their biosynthesis of new natural products.

Professor Tim Stinear, Department of Microbiology and Immunology, The University of Melbourne; The Peter Doherty Institute for Infection and Immunity

Professor Ben Howden, Department of Microbiology and Immunology, The University of Melbourne; The Peter Doherty Institute for Infection and Immunity

Associate Professor Torsten Seemann, Department of Microbiology and Immunology, The University of Melbourne; The Peter Doherty Institute for Infection and Immunity

Professor Mark Rizzacasa, School of Chemistry, Bio21 Molecular Science & Biotechnology Institute, The University of Melbourne

Professor Christian Hertweck, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI), Jena, Germany

Professor Helge Bode, Goethe University, Frankfurt, Germany