Bogland plant Tormentil inhibits multidrug-resistant pathogen growth and potentiates antibiotics by disrupting iron homeostasis

The antibiotic resistance crisis has created an urgent need for the development of novel therapeutic strategies to tackle recalcitrant infections. In this study, we identified Tormentil [<i>Potentilla erecta</i> (L.) Raeusch.], a plant that has been used in traditional medicine for centuries, as being capable of effectively inhibiting the growth of carbapenem-resistant <i>Acinetobacter baumannii</i>. We identified agrimoniin and ellagic acid as two bioactive components with antibacterial activity present within Tormentil extracts. Combinatorial RNA-seq analysis revealed that these compounds were able to inhibit the growth of <i>A. baumannii</i> by disrupting intracellular iron homeostasis, an effect that could be reversed through exogenous iron supplementation. We also demonstrated that Tormentil could potentiate the activity of the last-resort antibiotic, colistin. Overall, these findings valorize the centuries-old traditional use of Tormentil to treat infection and highlight how its bioactive constituents could be exploited to prolong the lifespan of our last line of antibiotic defence, colistin.