start-ver=1.4
cd-journal=joma
no-vol=10
cd-vols=
no-issue=1
article-no=
start-page=10876
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200702
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The role of RND-type efflux pumps in multidrug-resistant mutants of Klebsiella pneumoniae
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The emergence of multidrug-resistant Klebsiella pneumoniae is a worldwide problem. K. pneumoniae possesses numerous resistant genes in its genome. We isolated mutants resistant to various antimicrobials in vitro and investigated the importance of intrinsic genes in acquired resistance. The isolation frequency of the mutants was 10(-7)-10(-9). Of the multidrug-resistant mutants, hyper-multidrug-resistant mutants (EB256-1, EB256-2, Nov1-8, Nov2-2, and OX128) were identified, and accelerated efflux activity of ethidium from the inside to the outside of the cells was observed in these mutants. Therefore, we hypothesized that the multidrug efflux pump, especially RND-type efflux pump, would be related to changes of the phenotype. We cloned all RND-type multidrug efflux pumps from the K. pneumoniae genome and characterized them. KexEF and KexC were powerful multidrug efflux pumps, in addition to AcrAB, KexD, OqxAB, and EefABC, which were reported previously. It was revealed that the expression of eefA was increased in EB256-1 and EB256-2: the expression of oqxA was increased in OX128; the expression of kexF was increased in Nov2-2. It was found that a region of 1,485 bp upstream of kexF, was deleted in the genome of Nov2-2. K. pneumoniae possesses more potent RND-multidrug efflux systems than E. coli. However, we revealed that most of them did not contribute to the drug resistance of our strain at basic levels of expression. On the other hand, it was also noted that the overexpression of these pumps could lead to multidrug resistance based on exposure to antimicrobial chemicals. We conclude that these pumps may have a role to maintain the intrinsic resistance of K. pneumoniae when they are overexpressed. The antimicrobial chemicals selected many resistant mutants at the same minimum inhibitory concentration (MIC) or a concentration slightly higher than the MIC. These results support the importance of using antibiotics at appropriate concentrations at clinical sites.
en-copyright=
kn-copyright=

en-aut-name=NiRui Ting
en-aut-sei=Ni
en-aut-mei=Rui Ting
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=OnishiMotoyasu
en-aut-sei=Onishi
en-aut-mei=Motoyasu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MizusawaMinako
en-aut-sei=Mizusawa
en-aut-mei=Minako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KitagawaRyoko
en-aut-sei=Kitagawa
en-aut-mei=Ryoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KishinoTakanori
en-aut-sei=Kishino
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MatsubaraFutoshi
en-aut-sei=Matsubara
en-aut-mei=Futoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TsuchiyaTomofusa
en-aut-sei=Tsuchiya
en-aut-mei=Tomofusa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KurodaTeruo
en-aut-sei=Kuroda
en-aut-mei=Teruo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=OgawaWakano
en-aut-sei=Ogawa
en-aut-mei=Wakano
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Microbiology, Faculty of Pharmaceutical Sciences,Okayama University
kn-affil=

affil-num=5
en-affil=Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Microbiology and Biochemistry, Daiichi University of Pharmacy
kn-affil=

affil-num=7
en-affil=Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=9
en-affil=Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Antimicrobial resistance
kn-keyword=Antimicrobial resistance
en-keyword=Bacteria
kn-keyword=Bacteria
en-keyword=Bacteriology
kn-keyword=Bacteriology
END

start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=
article-no=
start-page=4854
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=2019319
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Comprehensive analysis of resistance-nodulation-cell division superfamily (RND) efflux pumps from Serratia marcescens, Db10
en-subtitle=
kn-subtitle=
en-abstract=
kn-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 coil. 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 6G efflux assay. When expressed in the toiC-deficient strain of E. coil, KAM43, none of the genes conferred resistance on E. coil. When hasF, encoding the S. marcescens ToIC ortholog, was expressed in KAM43, all of the genes conferred resistance on E. coil, 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.
en-copyright=
kn-copyright=

en-aut-name=TobaShinsuke
en-aut-sei=Toba
en-aut-mei=Shinsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MinatoYusuke
en-aut-sei=Minato
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KondoYuma
en-aut-sei=Kondo
en-aut-mei=Yuma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=HoshikawaKanami
en-aut-sei=Hoshikawa
en-aut-mei=Kanami
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MinagawaShu
en-aut-sei=Minagawa
en-aut-mei=Shu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KomakiShiho
en-aut-sei=Komaki
en-aut-mei=Shiho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KumagaiTakanori
en-aut-sei=Kumagai
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=MatobaYasuyuki
en-aut-sei=Matoba
en-aut-mei=Yasuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MoritaDaichi
en-aut-sei=Morita
en-aut-mei=Daichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=OgawaWakano
en-aut-sei=Ogawa
en-aut-mei=Wakano
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=GotohNaomasa
en-aut-sei=Gotoh
en-aut-mei=Naomasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=TsuchiyaTomofusa
en-aut-sei=Tsuchiya
en-aut-mei=Tomofusa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=KurodaTeruo
en-aut-sei=Kuroda
en-aut-mei=Teruo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil= Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil= Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Microbiology, Institute of Biomedical & Health Sciences, Hiroshima University
kn-affil=

affil-num=4
en-affil= Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=
kn-affil=

affil-num=6
en-affil= Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Microbiology, Institute of Biomedical & Health Sciences, Hiroshima University
kn-affil=

affil-num=8
en-affil=Department of Microbiology, Institute of Biomedical & Health Sciences, Hiroshima University
kn-affil=

affil-num=9
en-affil=Department of Microbiology, Institute of Biomedical & Health Sciences, Hiroshima University
kn-affil=

affil-num=10
en-affil= Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=11
en-affil= Department of Microbiology and Infection Control Science, Kyoto Pharmaceutical University
kn-affil=

affil-num=12
en-affil= Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=13
en-affil=Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2003
dt-pub=20030930
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=細菌細胞におけるイオン共役型輸送系の解析
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=OgawaWakano
en-aut-sei=Ogawa
en-aut-mei=Wakano
kn-aut-name=小川和加野
kn-aut-sei=小川
kn-aut-mei=和加野
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学
END