Structural and functional studies of iron uptake ATP-binding cassette transporters (ABC transporters) in Gram-negative bacteria
| Project/Area Number |
20K22561
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0601:Agricultural chemistry and related fields
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Lu Peng 東京大学, 大学院農学生命科学研究科(農学部), 助教 (20880339)
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| Project Period (FY) |
2020-09-11 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | FbpA / vibriosis / spice extracts / rosmarinic acid / Vibrio species / bacteriostatic agent / VmFbpA / Membrane Protein / ABC transporter / Vibrio. species / Iron / Vibrio. spp / iron / Vibrio spp |
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| Outline of Research at the Start |
1) To reveal the Fe3+-binding and release mechanisms of FbpA.
2) To determine the structures of FbpBC and FbpBC-A complexes.
3) To inhibit the growth of Vibrio spp. based on iron restriction via the inhibition of FbpA.
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| Outline of Final Research Achievements |
Food ingredients screening from hot water extracts of spices and herbs that specifically inhibit iron binding of PBP (FbpA) from Vibrio. metschnikovii were performed and a compound, rosmarinic acid (RA), from rosemary extracts was identified as an inhibitor of iron uptake. The bacteriostatic activity of RA was confirmed and can be enhanced in the presence of sodium citrate (SC). The crystal structure of RA bound to the iron-binding site of FbpA from V. metschnikovii was solved and the mechanism of iron uptake inhibition was revealed at the molecular level. Moreover, bacteriostatic activity of RA and SC can also be overserved in other pathogenic vibrio species (e.g. V. parahaemolyticus, V. alginolyticus, and V. vulnificus).
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| Academic Significance and Societal Importance of the Research Achievements |
学術的意義：ビブリオ菌由来の鉄結合タンパク質FbpAの構造解析によって、菌のFe3+取り込み機構を明らかにした。更に、FbpAを阻害する機構を持つロスマリン酸（RA）との複合体の構造解析により、その分子機構も可視化できた。
社会的意義：本研究から得られるビブリオ属細菌に対する静菌剤は、ヒトにとって安全な食品成分からなり、抗菌スペクトルが狭く選択的な静菌作用を示した。食品生産、保管、流通における使用だけでなく、消費者も安心して利用可能である。畜産・水産・植物栽培、ヒト医療・獣医医療における抗生物質の過剰・不適切な使用を減らすことに貢献する。
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Report
(3 results)
Research Products
(3 results)
