Leveraging antibiotic hormesis for cryptic natural product discovery

Area of Science:

• Microbiology
• Natural Product Chemistry
• Drug Discovery

Background:

• Microbial natural products are crucial for therapeutics.
• Many are inaccessible due to low gene expression in lab settings.

Purpose of the Study:

• To develop a screening approach for discovering inaccessible microbial natural products.
• To utilize antibiotic hormesis for eliciting secondary metabolites.

Main Methods:

• Generated a library of clinical antibiotics.
• Applied high-dose inhibition and low-dose stimulation assays on diverse bacteria.
• Performed scale-up fermentation and metabolomic analysis.

Main Results:

• Induced cryptic metabolites in all tested bacterial strains.
• Identified 9 new natural products and 8 known cryptic metabolites.
• Demonstrated the broad applicability of antibiotic hormesis.

Conclusions:

• Antibiotic hormesis is a rapid and scalable platform for natural product discovery.
• Low-dose antibiotics are effective signaling molecules for metabolite production.
• This work facilitates further research into cryptic metabolite biosynthesis.