# Drosera rotundifolia L. as E. coli biofilm inhibitor: Insights into the mechanism of action using proteomics/metabolomics and toxicity studies

## TL;DR

This study shows that compounds from the sundew plant can inhibit E. coli biofilms and suggests how they work, while confirming their safety.

## Contribution

The study reveals the molecular mechanisms by which sundew compounds inhibit E. coli biofilms using proteomic and metabolomic approaches.

## Key findings

- Flavonoids inhibit biofilm formation by iron chelation and altering polyamine balance.
- Naphthoquinones affect stress response pathways and the regulatory protein OmpR.
- Toxicity tests confirm the safety of Drosera extracts in 3D cell cultures and Galleria mellonella.

## Abstract

The successful sustainable cultivation of the well-known medicinal plant sundew on rewetted peatlands not only leads to the preservation of natural populations, but also provides a basis for the sustainable pharmaceutical use of the plant. The bioactive compounds of sundew, flavonoids and naphthoquinones, show biofilm-inhibiting properties against multidrug-resistant, ESBL-producing E. coli strains and open up new therapeutic possibilities.

This study investigates the molecular mechanisms of these compounds in biofilm inhibition through proteomic analyses. Specific fractions of flavonoids and naphthoquinones, as well as individual substances like 7-methyljuglone and 2″-O-galloylhyperoside, are analyzed. Results show that naphthoquinones appear to act via central regulatory proteins such as OmpR and alter the stress response while flavonoids likely affect biofilm formation by creating an iron-poor environment through iron complexation and additionally influence polyamine balance, reducing intracellular spermidine levels. Further investigations including assays for iron complexation and analysis of polyamines confirmed the proteomic data. Safety evaluations through cytotoxicity tests in 3D cell cultures and the Galleria mellonella in vivo model confirm the safety of the extracts used. These findings highlight sundew as a promising candidate for new phytopharmaceuticals.

•Flavonoids and naphthoquinones from Drosera inhibit biofilm formation in ESBL-E. coli.•Proteome and metabolome analyses suggest a potential mechanism of action.•Flavonoids may inhibit biofilm formation through iron chelation and polyamine balance.•Naphthoquinones show effects on stress response pathways and biofilm regulatory point OmpR.•In vitro toxicity tests and Galleria mellonella model confirm the safety of Drosera extracts.

Flavonoids and naphthoquinones from Drosera inhibit biofilm formation in ESBL-E. coli.

Proteome and metabolome analyses suggest a potential mechanism of action.

Flavonoids may inhibit biofilm formation through iron chelation and polyamine balance.

Naphthoquinones show effects on stress response pathways and biofilm regulatory point OmpR.

In vitro toxicity tests and Galleria mellonella model confirm the safety of Drosera extracts.