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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 publons researchmap
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.
Keywords
Antimicrobial resistance
Bacteria
Bacteriology
Published Date
2020-07-02
Publication Title
Scientific Reports
Volume
volume10
Issue
issue1
Publisher
Nature
Start Page
10876
ISSN
2045-2322
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
© The Author(s) 2020
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DOI
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isVersionOf https://doi.org/10.1038/s41598-020-67820-x
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http://creat iveco mmons .org/licen ses/by/4.0/
Funder Name
Ministry of Education, Culture, Sports, Science and Technology
助成番号
22590064