Structure and function relationship of OqxB efflux pump from Klebsiella pneumoniae

Nat Commun. 2021 Sep 13;12(1):5400. doi: 10.1038/s41467-021-25679-0.


OqxB is an RND (Resistance-Nodulation-Division) efflux pump that has emerged as a factor contributing to the antibiotic resistance in Klebsiella pneumoniae. OqxB underwent horizontal gene transfer and is now seen in other Gram-negative bacterial pathogens including Escherichia coli, Enterobacter cloacae and Salmonella spp., further disseminating multi-drug resistance. In this study, we describe crystal structure of OqxB with n-dodecyl-β-D-maltoside (DDM) molecules bound in its substrate-binding pocket, at 1.85 Å resolution. We utilize this structure in computational studies to predict the key amino acids contributing to the efflux of fluoroquinolones by OqxB, distinct from analogous residues in related transporters AcrB and MexB. Finally, our complementation assays with mutated OqxB and minimum inhibitory concentration (MIC) experiments with clinical isolates of E. coli provide further evidence that the predicted structural features are indeed involved in ciprofloxacin efflux.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Binding Sites / genetics
  • Crystallography, X-Ray
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Klebsiella pneumoniae / genetics*
  • Klebsiella pneumoniae / metabolism
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / genetics*
  • Membrane Transport Proteins / metabolism
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Protein Binding
  • Protein Conformation
  • Protein Multimerization
  • Structure-Activity Relationship


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Membrane Transport Proteins

Associated data

  • figshare/10.6084/m9.figshare.15089934.v1
  • figshare/10.6084/m9.figshare.15090153.v1
  • figshare/10.6084/m9.figshare.15090162.v1
  • figshare/10.6084/m9.figshare.15090189.v1
  • figshare/10.6084/m9.figshare.15090249.v1
  • figshare/10.6084/m9.figshare.15090210.v1