Mining and expressing novel antimicrobials from sponge symbionts

Project

Mining and expressing novel antimicrobials from sponge symbionts

Mine deep-sea sponge symbionts, which are “mare incognita” with respect to their bioactive potential, and develop a heterologous expression strategy for the gene clusters producing antimicrobials.

Antibiotic resistant (ABR) bacteria are estimated to cause >25,000 deaths annually in Europe alone, and the ABR problem is intertwined with the decreasing discovery rate of new antimicrobials. A promising strategy to re-tap the reservoir of natural antimicrobials is to shift focus to the marine environment and marine sponge-associated bacteria excrete a plethora of metabolic compounds with potential as novel clinical antimicrobials. Important enzyme complexes producing these natural drug candidates are non-ribosomal peptides synthetases (NRPS) and type I polyketide synthases (PKS). These compounds have been shown to interfere with pathogenesis and have potential as novel antimicrobial structures. This project aims to screen for these molecules in deep-sea sponge symbionts, which are “mare incognita” with respect to their bioactive potential, and to develop a heterologous expression strategy for the gene clusters producing the antimicrobials, thus creating a novel production platform for targeted compounds originating from uncultivable microbes. Finally, we will integrate the search for antimicrobials with their applicability to inhibit relevant disease causing gut-associated pathogens.