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ID 116302
著者
Watanabe, Kaori Kumamoto University
Chuang, Victor T. G. Monash University Malaysia
Takeda, Iyo Kumamoto University
Kuroda, Teruo Hiroshima University
Ogawa, Wakano Daiichi University of Pharmacy
Watanabe, Hiroshi Kumamoto University
Iwao, Yasunori University of Shizuoka
Otagiri, Masaki Sojo University
Maruyama, Toru Kumamoto University
キーワード
alpha‐1‐acid glycoprotein
antimicrobial effect
multidrug resistance
nitric oxide
S‐nitrosation
資料タイプ
学術雑誌論文
抄録
Alpha-1-acid glycoprotein (AGP) is a major acute-phase protein. Biosynthesis of AGP increases markedly during inflammation and infection, similar to nitric oxide (NO) biosynthesis. AGP variant A (AGP) contains a reduced cysteine (Cys149). Previously, we reported that S-nitrosated AGP (SNO-AGP) synthesized by reaction with a NO donor, possessed very strong broad-spectrum antimicrobial activity (IC50 = 10−9-10−6 M). In this study, using a cecal ligation and puncture animal model, we confirmed that AGP can be endogenously S-nitrosated during infection. Furthermore, we examined the antibacterial property of SNO-AGP against multidrug-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa to investigate the involvement of SNO-AGP in the host defense system. Our results showed that SNO-AGP could inhibit multidrug efflux pump, AcrAB-TolC, a major contributor to bacterial multidrug resistance. In addition, SNO-AGP decreased biofilm formation and ATP level in bacteria, indicating that SNO-AGP can revert drug resistance. It was also noteworthy that SNO-AGP showed synergistic effects with the existing antibiotics (oxacillin, imipenem, norfloxacin, erythromycin, and tetracycline). In conclusion, SNO-AGP participated in the host defense system and has potential as a novel agent for single or combination antimicrobial therapy.
掲載誌名
FASEB BioAdvances
ISSN
25739832
出版者
Federation of American Societies for Experimental Biology|Wiley
1
3
開始ページ
137
終了ページ
150
発行日
2018-09-01
権利情報
This is an open access article under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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出版社版DOI
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フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
薬学系