Harnessing Molecular and Bioactivity Network Analysis to Prioritize Antibacterial Compound Isolation From...

Area of Science:

• Mycology
• Natural Product Chemistry
• Antimicrobial Drug Discovery

Background:

• Antimicrobial resistance poses a significant global health threat, necessitating novel bioactive compound development.
• Fungal metabolites represent a promising, yet underexplored, resource for discovering new antimicrobial agents.

Purpose of the Study:

• To investigate the metabolic profiles of micromycetes associated with Mexican cloud forest ants.
• To isolate and characterize antibacterial compounds from these fungi using network analysis.
• To evaluate the bioactivity of isolated compounds against drug-resistant bacteria.

Main Methods:

• Cultured 248 fungal strains from ants and soil.
• Assessed in vitro inhibition of Acinetobacter baumannii and Klebsiella pneumoniae.
• Utilized molecular networking and compound activity mapping for metabolite analysis.
• Isolated and structurally elucidated compounds using spectroscopic methods.

Main Results:

• Dereplicated 15 secondary metabolites and isolated 10 compounds, including a new polyol (25).
• Identified compounds 16-18 as bioactive, with deoxy-PF1140 (16) and PF1140 (17) showing first-reported antibacterial activity against Acinetobacter baumannii.
• Achieved minimum inhibitory concentrations of 50 μg/mL for compounds 16 and 17.

Conclusions:

• Network analysis and dereplication are effective strategies for bioprospecting antibacterial fungal metabolites.
• This study highlights the chemical diversity of cloud forest soil fungi and their potential in drug discovery.
• Expanded knowledge of fungal secondary metabolites associated with specific ant species.