Structural basis for spermidine recognition and modulation of <i>Acinetobacter baumannii</i> multidrug efflux regulator AmvR

Multidrug efflux pumps are key contributors to clinically significant drug resistance in various gram-negative pathogens responsible for hospital-acquired infections. These pathogens often possess multiple genes that encode potential multidrug efflux pumps. Identifying the specific regulatory proteins that control the expression of these pumps, along with elucidating the regulatory mechanisms triggered by effectors, presents a complex challenge. In this study, we have resolved the crystal structures of AmvR in both its unbound and spermidine-bound states. To the best of our knowledge, this represents the first validated structural model of a polyamine-bound transcriptional regulator. Through detailed structural analysis and functional assays, we have pinpointed the critical residues in AmvR responsible for substrate recognition, providing a foundation for the development of future inhibitors.