Short Lecture "A high-throughput and cost-effective metabolomic based platform to overcome natural products screening limitations for antimicrobial drug discovery"

Antimicrobial resistance (AMR) is a major global health crisis and one way to tackle this issue is the imperative discovery of new antimicrobial compounds. In this context, microbial natural products have proven to possess very potent activities. However, the cultivation of microorganisms is a slow process and the frequent isolation of known antimicrobial compounds is a limitation when screening natural extracts. To circumvent this, we recently developed a drug discovery platform and applied it to a large collection of fungi. Culture, extraction, bioassays and metabolomics were performed in the standardised 96-well plate format thus allowing a high-throughput and compatibility across the platforms. All fungal extracts were enriched by solid phase extraction (SPE) and systematically submitted to antimicrobial bioassays and metabolomic profiling. All the generated data were incorporated into a massive and multi-informative molecular network that is the core of our natural products prioritisation strategy to rapidly highlight potentially bioactive scaffolds within the chemical diversity of crude extracts collections. This study demonstrates the efficiency of our method to: 1) rapidly dereplicate known antimicrobial compounds (Verticilium lateritium to Chaetocin); 2) identify a hit and screen dozens of congeners to find a better producer and evaluate the best culture conditions prior to scale-up (Penicillium expansum), and 3) select an interesting hit for scale-up and compound isolation (Phialophora gregata). Our approach not only minimises the risk of rediscovering known compounds but also provides a streamlined and cost-effective way to accelerate the discovery of new antimicrobial agents and contribute to the fight against AMR ([Fig. 1]).

Fig. 1 General workflow description.

Publikationsverlauf

Artikel online veröffentlicht:
16. November 2023