Cryoelectron Microscopy Structures of AdeB Illuminate Mechanisms of Simultaneous Binding and Exporting of Substrates
Christopher E. Morgan, Przemysław Glaza, Inga V. Leus, Anhthu Trinh, Chih‐Chia Su, Meng Cui, Helen I. Zgurskaya, Edward Yu
Abstract
has emerged as one of the most highly antibiotic-resistant Gram-negative pathogens. The prevalent AdeB multidrug efflux pump mediates resistance to a broad spectrum of clinically relevant antimicrobial agents. Here, we report six cryo-EM structures of the trimeric AdeB pump in the presence of ethidium bromide. We discover that a single AdeB protomer can simultaneously anchor a number of ligands, and different AdeB protomers can bind ethidium molecules simultaneously. The results indicate that each AdeB protomer within the trimer recognizes and extrudes drugs independently.
Topics & Concepts
Acinetobacter baumanniiEffluxMicrobiologyAntimicrobialAntibiotic resistanceNeisseriaceaeAcinetobacterBroad spectrumMultiple drug resistanceComputational biologyAntibioticsBiologyBacteriaChemistryGeneticsPseudomonas aeruginosaCombinatorial chemistryAntibiotic Resistance in BacteriaEscherichia coli research studiesEnterobacteriaceae and Cronobacter Research