Abstract

We investigated the role of the resistance-nodulation-cell division superfamily (RND) efflux system on intrinsic multidrug resistance in Serratia marcescens. We identified eight putative RND efflux system genes in the S. marcescens Db10 genome that included the previously characterized systems, sdeXY, sdeAB, and sdeCDE. Six out of the eight genes conferred multidrug resistance on KAM32, a drug hypersensitive strain of Escherichia coli. Five out of the eight genes conferred resistance to benzalkonium, suggesting the importance of RND efflux systems in biocide resistance in S. marcescens. The energy-dependent efflux activities of five of the pumps were examined using a rhodamine 6 G efflux assay. When expressed in the tolC-deficient strain of E. coli, KAM43, none of the genes conferred resistance on E. coli. When hasF, encoding the S. marcescens TolC ortholog, was expressed in KAM43, all of the genes conferred resistance on E. coli, suggesting that HasF is a major outer membrane protein that is used by all RND efflux systems in this organism. We constructed a sdeXY deletion mutant from a derivative strain of the clinically isolated multidrug-resistant S. marcescens strain and found that the sdeXY deletion mutant was sensitive to a broad spectrum of antimicrobial agents.

Details

Title
Comprehensive analysis of resistance-nodulation-cell division superfamily (RND) efflux pumps from Serratia marcescens, Db10
Author
Toba Shinsuke 1 ; Minato Yusuke 2   VIAFID ORCID Logo  ; Kondo Yuma 3 ; Hoshikawa Kanami 1 ; Minagawa Shu 4 ; Komaki Shiho 1 ; Kumagai Takanori 3 ; Matoba Yasuyuki 3 ; Morita Daichi 3 ; Ogawa Wakano 5 ; Gotoh Naomasa 4 ; Tsuchiya Tomofusa 1 ; Kuroda Teruo 6 

1  Dentistry and Pharmaceutical Sciences, Okayama University, Department of Microbiology, Graduate School of Medicine, Tsushima, Japan (GRID:grid.261356.5) (ISNI:0000 0001 1302 4472) 
2  Dentistry and Pharmaceutical Sciences, Okayama University, Department of Microbiology, Graduate School of Medicine, Tsushima, Japan (GRID:grid.261356.5) (ISNI:0000 0001 1302 4472); University Minnesota Medical School, Department of Microbiology and Immunology, Minneapolis, USA (GRID:grid.17635.36) (ISNI:0000000419368657) 
3  Hiroshima University, Department of Microbiology, Institute of Biomedical & Health Sciences, Minami-ku, Japan (GRID:grid.257022.0) (ISNI:0000 0000 8711 3200) 
4  Kyoto Pharmaceutical University, Department of Microbiology and Infection Control Science, Yamashina-ku, Japan (GRID:grid.411212.5) (ISNI:0000 0000 9446 3559) 
5  Dentistry and Pharmaceutical Sciences, Okayama University, Department of Microbiology, Graduate School of Medicine, Tsushima, Japan (GRID:grid.261356.5) (ISNI:0000 0001 1302 4472); Daiichi University of Pharmacy, Department of Microbiology and Biochemistry, Minami-ku, Japan (GRID:grid.417740.1) (ISNI:0000 0004 0370 1830) 
6  Dentistry and Pharmaceutical Sciences, Okayama University, Department of Microbiology, Graduate School of Medicine, Tsushima, Japan (GRID:grid.261356.5) (ISNI:0000 0001 1302 4472); Hiroshima University, Department of Microbiology, Institute of Biomedical & Health Sciences, Minami-ku, Japan (GRID:grid.257022.0) (ISNI:0000 0000 8711 3200) 
Publication year
2019
Publication date
Dec 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-019-41237-7
ProQuest document ID
2194123909
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.