Innovative antimicrobial discovery from proprietary strains

Overview

This research initiative focuses on the discovery of novel antimicrobial compounds from proprietary strains, hypothesized to produce unique polypeptides, bacteriocins, or small molecules. Leveraging the prolific antimicrobial-producing capabilities of actinobacteria, particularly from the genus Streptomyces, this project aims to expand the arsenal of antimicrobial agents effective against resistant pathogens. The anticipated outcomes include the identification and characterization of compounds capable of outcompeting harmful species, thereby addressing the growing threat of antimicrobial resistance.

Technical specifications

The research employs a comprehensive approach to identify potential antimicrobial compounds:

• Genome Sequencing and Analysis: Utilize antiSMASH for genome sequencing to identify biosynthetic gene clusters.
• Induction of Metabolite Production: Cultivate strains on various media to stimulate secondary metabolite production.
• Activity-Guided Fractionation: Extract and screen metabolites using solvent extraction followed by activity-guided fractionation.
• Structural Elucidation: Apply NMR techniques guided by structural predictions from miBIG to solve compound structures.
• Pathogen Testing: Conduct assays on purified compounds against ESKAPE pathogens and extend testing to clinical isolates.
• Genetic Validation: Implement gene deletion strategies to confirm the role of specific gene clusters in compound production.
• Heterologous Expression: Clone and express gene clusters in super host strains to validate production pathways.

Technology readiness level

The project is currently at Technology Readiness Level 2, indicating that the concept has been formulated and research is underway to validate the hypothesis through laboratory experimentation and initial testing.