ID | 60273 |
フルテキストURL | |
著者 |
Ni, Rui Ting
Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Onishi, Motoyasu
Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mizusawa, Minako
Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kitagawa, Ryoko
Department of Microbiology, Faculty of Pharmaceutical Sciences,Okayama University
Kishino, Takanori
Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Matsubara, Futoshi
Department of Microbiology and Biochemistry, Daiichi University of Pharmacy
Tsuchiya, Tomofusa
Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kuroda, Teruo
Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Ogawa, Wakano
Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kaken ID
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抄録 | 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.
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キーワード | Antimicrobial resistance
Bacteria
Bacteriology
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発行日 | 2020-07-02
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出版物タイトル |
Scientific Reports
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巻 | 10巻
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号 | 1号
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出版者 | Nature
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開始ページ | 10876
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ISSN | 2045-2322
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © The Author(s) 2020
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論文のバージョン | publisher
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PubMed ID | |
DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.1038/s41598-020-67820-x
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ライセンス | http://creat iveco mmons .org/licen ses/by/4.0/
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助成機関名 |
文部科学省
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助成番号 | 22590064
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