Structure and function relationship of OqxB efflux pump from Klebsiella pneumoniae

Nagakumar Bharatham, Purnendu Bhowmik, Maho Aoki, Ui Okada, Sreevalli Sharma, Eiki Yamashita, Anirudh P. Shanbhag, Sreenath Rajagopal, Teby Thomas, Maitrayee Sarma, Riya Narjari, Savitha Nagaraj, Vasanthi Ramachandran, Nainesh Katagihallimath, Santanu Datta and Satoshi Murakami ()
Additional contact information
Nagakumar Bharatham: Bugworks Research India Pvt. Ltd., Centre for Cellular and Molecular Platforms, GKVK, Bellary Rd
Purnendu Bhowmik: Bugworks Research India Pvt. Ltd., Centre for Cellular and Molecular Platforms, GKVK, Bellary Rd
Maho Aoki: Tokyo Institute of Technology
Ui Okada: Tokyo Institute of Technology
Sreevalli Sharma: Bugworks Research India Pvt. Ltd., Centre for Cellular and Molecular Platforms, GKVK, Bellary Rd
Eiki Yamashita: Osaka University, Suita
Anirudh P. Shanbhag: Bugworks Research India Pvt. Ltd., Centre for Cellular and Molecular Platforms, GKVK, Bellary Rd
Sreenath Rajagopal: Bugworks Research India Pvt. Ltd., Centre for Cellular and Molecular Platforms, GKVK, Bellary Rd
Teby Thomas: St. John’s Research Institute
Maitrayee Sarma: Bugworks Research India Pvt. Ltd., Centre for Cellular and Molecular Platforms, GKVK, Bellary Rd
Riya Narjari: Bugworks Research India Pvt. Ltd., Centre for Cellular and Molecular Platforms, GKVK, Bellary Rd
Savitha Nagaraj: St. John’s Medical Hospital
Vasanthi Ramachandran: Bugworks Research India Pvt. Ltd., Centre for Cellular and Molecular Platforms, GKVK, Bellary Rd
Nainesh Katagihallimath: Bugworks Research India Pvt. Ltd., Centre for Cellular and Molecular Platforms, GKVK, Bellary Rd
Santanu Datta: Bugworks Research India Pvt. Ltd., Centre for Cellular and Molecular Platforms, GKVK, Bellary Rd
Satoshi Murakami: Tokyo Institute of Technology

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25679-0

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DOI: 10.1038/s41467-021-25679-0

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