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ID 111094
Title Alternative
緑膿菌クオラムセンシングオートインデューサー類似化合物は耐性菌に対し抗菌薬の活性を増強する
Enhancement activity of QS autoinducer analog
Author
Kariyama, Reiko Okayama University|Okayama Gakuin University
Hori, Kenji Okayama University
Irie, Yasuhiko University of Dayton
Viducic, Darija Tokushima University
Igarashi, Jun Otsuka Chemical
Suga, Hiroaki the University of Tokyo
Kumon, Hiromi Okayama University
Keywords
Pseudomonas aeruginosa
CRE
antibiotic resistance
Content Type
Thesis or Dissertation
Description
In this study, we have investigated the effects of the newly synthesized analog of Pseudomonas aeruginosa quorum-sensing autoinducer named AIA-1 (autoinducer analog) against antibiotic-resistant bacteria. In vitro susceptibility and killing assays for P. aeruginosa PAO1ΔoprD mutant and clinical isolates were performed by using antibiotics and AIA-1. In an in vivo assay, a luminescent carbapenem-resistant strain derived from PAO1ΔoprD was injected into neutropenic ICR mice and bioluminescence images were acquired after the treatment with antibiotics and AIA-1. Additionally, we investigated the effects of the combination use against carbapenem- resistant Enterobacteriaceae (CRE). Using killing assays in P. aeruginosa, the survival rates in the presence of antibiotics and AIA-1 significantly decreased in comparison with those with antibiotics alone. Furthermore, dual treatment of biapenem and AIA-1 was more effective than biapenem alone in a mouse infection model. AIA-1 did not change the MICs in P. aeruginosa, suggesting that AIA-1 acts on the mechanism of antibiotic tolerance. Conversely, the MICs of antibiotics decreased in the presence of AIA-1 in some CRE strains, indicating that AIA-1 may require additional mechanism to act on CRE. In conclusion, AIA-1 may be a potent drug for clinical treatment of infections caused by antibiotic-resistant bacteria.
Journal Title
The Journal of Medical Investigation
ISSN
13496867
13431420
NCID
AA11166929
AA12022913
Publisher
Faculty of Medicine Tokushima University
Volume
64
Issue
1-2
Start Page
101
End Page
109
Sort Key
101
Published Date
2017-02
Remark
内容要旨・審査要旨・論文本文の公開:
内容要旨:LID201704261006.pdf
審査要旨:LID201704261007.pdf
論文本文:LID201704261008.pdf
本論文は,著者Takashi Amohの学位論文として提出され,学位審査・授与の対象となっている。
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3078号
Diploma Number
甲口第421号
Granted Date
2017-03-23
Degree Name
Doctor of Dental Science
Grantor
Tokushima University
departments
Oral Sciences