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Crystal structure of multidrug efflux transporter OqxB from Klebsiella pneumoniaeCrystal structure of multidrug efflux transporter OqxB from Klebsiella pneumoniae
Structural highlights
FunctionPublication Abstract from PubMedOqxB 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-beta-D-maltoside (DDM) molecules bound in its substrate-binding pocket, at 1.85 A 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. Structure and function relationship of OqxB efflux pump from Klebsiella pneumoniae.,Bharatham N, Bhowmik P, Aoki M, Okada U, Sharma S, Yamashita E, Shanbhag AP, Rajagopal S, Thomas T, Sarma M, Narjari R, Nagaraj S, Ramachandran V, Katagihallimath N, Datta S, Murakami S Nat Commun. 2021 Sep 13;12(1):5400. doi: 10.1038/s41467-021-25679-0. PMID:34518546[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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