Differential induction of fusaric acid in the endophytic fungus, Fusarium sp. (UST-UVG10) by three different media results to enhanced, variable anti-staphylococcal and antimycobacterial activity

The rise of drug-resistant pathogenic bacteria has enabled the discovery and innovative biotechnological production of antimicrobial substances. Among the widely used strategies to induce antimicrobial substances from fungi is the One Strain Many Compounds (OSMAC) approach where alteration of cultivation parameters are explored. Herein, we report a comparative study on the metabolic profile and antibacterial/antimycobacterial activity of the extracts obtained from the endophytic fungus Fusarium sp. (UST-UVG10) associated with the Philippine endemic Annonaceae plant Uvaria valderammensis using the OSMAC approach. Fusarium sp. (UST-UVG10) was fermented on three different media (Q6 ½, ZM ½, and YM 6.3) to obtain crude extracts for chemical profiling and antimicrobial activity assessments. Among the three extracts, only the ZM ½ extract exhibited strong inhibition against Staphylococcus aureus (ZOI = 13.85 mm). Evaluation of antituberculosis activity using the Microplate Alamar Blue Assay (MABA) showed the YM 6.3 extracts to exhibit inhibition against the fast-growing Mycobacterium tuberculosis H37Rv (MIC= 62.0 ug/mL). Metabolic profiling using liquid chromatography-high resolution electrospray ionization mass spectrometry followed by dereplication with Global Natural Product Social Molecular Networking (GNPS) and SIRIUS databases illustrated induction of the mycotoxin picolinic acid derivative, fusaric acid in ZM ½ and the fungal antibiotic cyclodepsipeptide beauvericin in YM6.3 extracts. Fusaric acid was isolated, characterized, and exhibited profound antibacterial activity against S. aureus (MIC = 1.30 ug/mL) with moderate antimycobacterial activity against M. tuberculosis H37Rv (MIC= 52.4 ug/mL). Overall, our study demonstrated correlative influence of culture medium components and relative abundance of specific antimicrobial compounds, establishing a potential platform for targeted metabolite production.