Development of a novel sterilization method of Pseudomonas aeruginosa by artificial heme acquisition proteins that inhibit its heme acquisition
| Project/Area Number |
18H02084
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 37010:Bio-related chemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
Shoji Osami 名古屋大学, 理学研究科, 教授 (90379587)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | ヘム獲得蛋白質 / 緑膿菌 / ポルフィリン / フタロシアニン / 光殺菌 / 増感剤 / 多剤耐性菌 / 結晶構造解析 / フタロシアニンシアニン / ヘム獲得タンパク質 / 金属錯体 / 殺菌 |
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| Outline of Final Research Achievements |
Pseudomonas aeruginosa, one of the more notorious opportunistic human pathogens, which has been classed with the highest priority level of “critical” by the World Health Organization (WHO). We demonstrated that bacterial heme transport systems can be exploited for the delivery of antimicrobials to the intracellular space of target bacteria with high specificity. We demonstrated that, analogous to heme uptake, HasA can specifically traffic an antimicrobial, gallium phthalocyanine (GaPc), into the intracellular space of Pseudomonas aeruginosa the interaction of HasA with its outer membrane receptor HasR. HasA enables water-insoluble GaPc to be mistakenly acquired by Pseudomonas aeruginosa, permitting its sterilization (>99.99%) by irradiation with near-infrared (NIR) light, irrespective of antibiotic resistance. This specific route of antimicrobial transport enables the efficient sterilization of P. aeruginosa, including its multidrug-resistant strains (MDRP).
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| Academic Significance and Societal Importance of the Research Achievements |
緑膿菌はヒトに日和見感染する病原菌であり，高い薬剤抵抗性や薬剤耐性化しやすい性質から，既存の抗生物質が効かない薬剤耐性緑膿菌が多く発生している．世界保健機関(WHO)は最も危険な薬剤耐性菌の1種としてカルバペネム系抗生物質に耐性化した緑膿菌をあげており，従来の抗菌薬とは作用機序が異なり耐性化されにくい，緑膿菌感染症の新たな治療法開発が強く望まれている．本研究では，日和見感染菌の緑膿菌を標的とし，合成金属錯体を内包させた人工金属蛋白質を構築し，従来の抗菌薬とは全く異なる作用機序の緑膿菌高選択的な光殺菌法を開発した．
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Report
(4 results)
Research Products
(43 results)
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[Journal Article] Highly malleable haem-binding site of the haemoprotein HasA permits stable accommodation of bulky tetraphenylporphycenes2019
Author(s)
Sakakibara,E.; Shisaka,Y.; Iwai, Y.; Yamada, S.; Uehara, H.; Tosha, T.; Sugimoto, H.; Shiro, Y.; Stanfield, J. K.; Ogawa, K.; Watanabe, Y.; Shoji, O.
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Journal Title
RSC Advances
Volume: 9(32)
Issue: 32
Pages: 18697-18702
DOI
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Peer Reviewed / Open Access
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[Book] 感染症2018
Author(s)
四坂勇磨、荘司長三
Total Pages
4
Publisher
株式会社協和企画
Related Report
