Development of Inhibitors of Biofilm Formation Using Inhibition of Polyamines

• Project/Area Number: 23658079
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Applied microbiology
• Research Institution: Kyoto Institute of Technology
• Principal Investigator: Suzuki Hideyuki 京都工芸繊維大学, 工芸科学研究科, 教授 (10202136)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: ポリアミン / プトレッシン / スペルミジン / 大腸菌 / バイオフィルム / トランスポーター / カダベリン

Outline of Final Research Achievements

We have shown that spermidine is essential for E. coli biofilm formation. In a strain lacking spermidine acetyltransferase, when spermidine was added to the medium, spermidine was not metabolized to acetylspermidine, so that the concentration of spermidine in the cells increased, and the amount of biofilm formed increased accordingly. It was revealed that a strain that could not synthesize spermidine and lacked the spermidine importer PotABCD took up spermidine and became PotFGHI, which was considered to be a spermidine transporter. Furthermore, it was clarified that the presence of PotD protein as well as spermidine is essential for biofilm formation.

Academic Significance and Societal Importance of the Research Achievements

尿路感染症やカテーテルを介した感染において病原菌がバイオフィルムを形成すると難治性に陥りやすく、バイオフィルム形成を阻害する薬剤は重要である。本研究成果は、バイオフィルム形成を阻害する薬剤開発のターゲットとしてPotDタンパク質が重要であることを明らかにした。

Research Products

• [Journal Article] Properties of putrescine uptake by PotFGHI and PuuP and their physiological significance in Escherichia coli. (2014)
  • Author(s): Terui, Y. et al.
  • Journal Title: Amino Acids Volume: 46 Issue: 3 Pages: 661-670
  • DOI: 10.1007/s00726-013-1517-x
  • Peer Reviewed
• [Journal Article] Upregulation of colonic luminal polyamines produced by intestinal microbiota delays senescence in mice. (2014)
  • Author(s): Kibe R, Kurihara S, Sakai Y, Suzuki H, Ooga T, Sawaki E, Muramatsu K, Nakamura A, Yamashita A, Kitada Y, Kakeyama M. Benno Y. Matsumoto M.
  • Journal Title: Sci Rep. Volume: 4 Issue: 1 Pages: 4548-4548
  • DOI: 10.1038/srep04548
  • Peer Reviewed
• [Journal Article] Putrescine importer PlaP contributes to swarming motility and urothelial cell invasion in Proteus mirabilis. (2013)
  • Author(s): S. Kurihara, Y. Sakai, H. Suzuki, A. Muth, O. Phanstiel, and P. N. Rather.
  • Journal Title: Journal of Biological Chemistry Volume: 288 Issue: 22 Pages: 15668-15676
  • DOI: 10.1074/jbc.m113.454090
  • Peer Reviewed
• [Journal Article] Regulation mechanism of the putrescine utilization pathway by the transcription factor PuuR in Escherichia coli K-12 (2012)
  • Author(s): N. Nemoto, S. Kurihara, Y. Kitahara, K. Asada, K. Kato, and H. Suzuki
  • Journal Title: Journal of Bacteriology Volume: (in press) Issue: 13 Pages: 3437-3447
  • DOI: 10.1128/jb.00097-12
  • Peer Reviewed
• [Presentation] Transcription regulation of puu genes by a transcriptional regulator PuuR in Escherichia coli. (2012)
  • Author(s): H. Suzuki, N. Nemoto, S. Kurihara, Y. Kitahara, K. Asada, and K. Kato.
  • Organizer: International Congress on “Polyamines Biological and Clinical Perspectives”
  • Place of Presentation: Istanbul Kultur University Istanbul, Turkey.
• [Presentation] Spermidine is required for biofilm formation in Escherichia coli. (2012)
  • Author(s): S. Kakegawa, and H. Suzuki.
  • Organizer: International Congress on “Polyamines Biological and Clinical Perspectives”
  • Place of Presentation: Istanbul Kultur University Istanbul, Turkey.
• [Presentation] 大腸菌におけるバイオフィルム形成とポリアミンの関係. (2011)
  • Author(s): 掛川苑美、鈴木秀之
  • Organizer: 第３回日本ポリアミン学会年会
  • Place of Presentation: さいたま市民会館おおみや
• [Presentation] 腸内細菌がつくりだすシンビオジェニック因子ポリアミン～その機能と生産最適化～.
  • Author(s): 栗原新、松本光晴、鈴木秀之、辨野義己.
  • Organizer: 2014年度日本農芸化学会大会
  • Place of Presentation: 川崎市・明治大学生田キャンパス
• [Presentation] 大腸菌におけるバイオフィルム形成とポリアミンの関係.
  • Author(s): 掛川苑美、鈴木秀之.
  • Organizer: 2014年度日本農芸化学会大会
  • Place of Presentation: 川崎市・明治大学生田キャンパス
• [Presentation] 大腸菌におけるプトレッシン生産法の開発.
  • Author(s): 古道紗斗里、鈴木秀之.
  • Organizer: 2014年度日本農芸化学会大会
  • Place of Presentation: 川崎市・明治大学生田キャンパス
• [Presentation] 細菌の細胞外シグナル分子としてのポリアミンとその輸送.
  • Author(s): 栗原新、鈴木秀之、Otto Phanstiel IV、Philip N. Rather.
  • Organizer: 日本ポリアミン学会年会
  • Place of Presentation: 銚子市・千葉科学大学
• [Presentation] 大腸菌におけるプトレッシン生産能の向上.
  • Author(s): 古道紗斗里、鈴木秀之.
  • Organizer: 日本ポリアミン学会年会
  • Place of Presentation: 銚子市・千葉科学大学
• [Presentation] 大腸菌のバイオフィルム形成に及ぼすプトレッシンインポーターPlaPとスペルミジンの影響.
  • Author(s): 掛川苑美、鈴木秀之.
  • Organizer: 日本ポリアミン学会年会
  • Place of Presentation: 銚子市・千葉科学大学
• [Presentation] 大腸菌におけるバイオフィルム形成とポリアミンの関係.
  • Author(s): 掛川苑美、鈴木秀之.
  • Organizer: 「ポリアミンと核酸の共進化」第12回合同シンポジウム
  • Place of Presentation: 東京都・東京慈恵会医科大学
• [Presentation] 細菌のポリアミントランスポーターとその生理的役割.
  • Author(s): 鈴木秀之、掛川苑美、栗原新
  • Organizer: 平成25年度日本農芸化学会大会 シンポジウム
  • Place of Presentation: 東北大学、仙台
  • Invited
• [Book] Bacterial polyamine transporters. In Polyamines: A universal molecular nexus for growth, survival and specialized metabolism. (2014)
  • Author(s): S. Kurihara, and H. Suzuki.
  • Publisher: Springer
• [Book] Polyamine catabolism in prokaryotes. In Polyamines: A universal molecular nexus for growth, survival and specialized metabolism. (2014)
  • Author(s): H. Suzuki, and S. Kurihara.
  • Publisher: Springer
• [Book] Microbial production of food ingredients, enzymes and nutraceuticals. (2013)
  • Author(s): H. Suzuki
  • Publisher: Woodhead Publishing
• [Book] Handbook of Proteolytic Enzymes. 3rd ed. Vol. 1 (2013)
  • Author(s): J. Hiratake, H. Suzuki, K. Fukuyama, K. Wada, and H. Kumagai.
  • Publisher: Academic Press