Identification of Antibacterial Agents with a Synergistic Effect in Pteris vittata L. by Exploration of Metabolome Data and Multivariate Analysis.

Introduction: In metalliferous ecosystems, bacteria could develop membrane efflux pumps to extrude heavy metals. Native plants, frequently exposed to such bacteria, may serve as rich chemical reservoirs for discovering potential antibacterial and/or resistance-modifying agents.

Objectives: This study aims to investigate the antibacterial properties of Pteris vittata L., a metal hyperaccumulator abundant in metal-rich environments, against Stenotrophomonas maltophilia K279a, an opportunistic nosocomial pathogen linked to severe respiratory tract infections.

Material and methods: A novel approach was used, employing the metabolome of P. vittata in a partial least squares regression model to predict the correlation between the whole chemical profile and activity. Marked compounds were then subjected to in vitro test for bactericidal and synergistic properties using broth dilution and time-kill assays.

Results: The multivariate analysis demonstrated a strong synergistic effect among a range of flavonoids compared to the individual responses. Notably, nine flavonoids were confirmed to reduce the minimum inhibitory concentration and minimal bactericidal concentration values of active compounds, cyanidin-3,5-O-diglucoside and perlagonin, from 64.0 and 108 μg/mL to 0.25 and 3.38 μg/mL, respectively.

Conclusion: These results provide insights into the possibility of combating clinical infections caused by S. maltophilia and highlight the potential of exploring new synergetic interactions among natural products as an alternative to the conventional bio-guided isolation strategy.