The mechanisms of antibiotic tolerance focusing on intracellular signaling substance c-di-GMP.

• Project/Area Number: 26462787
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: The University of Tokushima
• Principal Investigator: MURAKAMI Keiji 徳島大学, 大学院医歯薬学研究部(歯学系), 准教授 (10335804)
• Co-Investigator(Kenkyū-buntansha): 弘田 克彦 徳島大学, 大学院医歯薬学研究部(歯学系), 准教授 (60199130) ; 三宅 洋一郎 徳島大学, 大学院医歯薬学研究部(歯学系), 教授 (80136093)
• Co-Investigator(Renkei-kenkyūsha): KARIYAMA Reiko 岡山学院大学, 人間生活学部, 教授 (40112148)
• Research Collaborator: AMOH Takashi 徳島大学, 大学院医歯薬学研究部, 助教 (00803545)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 緑膿菌 / 抗菌薬抵抗性 / c-di-GMP / 付着 / 付着菌 / バイオフィルム / c-diGMP

Outline of Final Research Achievements

Floating bacteria attach to the solid surface and form biofilms after produceing extracellular polysaccharides. Infectious diseases caused by biofilms are chronic and refractory, but the cause is considered to be antibiotic tolerance. In this study, we showed that the psl genes, which are activated by surface adherence through elevated c-di-GMP levels, confer antibiotic tolerance.

Research Products

• [Int'l Joint Research] University of Zagreb(Croatia)
• [Int'l Joint Research] University of Dayton(米国)
• [Journal Article] The role of psl genes in antibiotic tolerance of adherent Pseudomonas aeruginosa. (2017)
  • Author(s): K. Murakami, T. ono, D. Viducic, Y. Somiya, R. Kariyama, K. Hori, T. Amoh, K. Hirota, H. Kumon, M. R. Parsek, Y. Miyake
  • Journal Title: Antimicrobial Agents and Chemotherapy Volume: in press
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Explorative gene analysis of antibiotic tolerance related genes in adherent and biofilm cells in Pseudomonas aeruginosa. (2017)
  • Author(s): K. Murakami, T. ono, Y. Noma, I. Minase, T. Amoh, Y. Irie, K. Hirota, Y. Miyake
  • Journal Title: Journal of Infection and Chemotherapy Volume: 23 Pages: 271-277
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Interplay between the quorum sensing regulator VqsR and the Pseudomonas quinolone signal in mediating carbapenem tolerance in Pseudomonas aeruginosa. (2017)
  • Author(s): D. Viducic, K. Murakami, T. Amoh, T. Ono, Y. Miyake
  • Journal Title: Research In Microbiology Volume: in press
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] RpoN modulates carbapenem tolerance in Pseudomonas aeruginosa through Pseudomonas quinolone signal and PqsE. (2016)
  • Author(s): D. Viducic, K. Murakami, T. Amoh, T. Ono, Y. Miyake
  • Journal Title: Animicrobial Agents and Chemotherapy Volume: 60 Pages: 5752-5764
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 新規化合物が緑膿菌の抗菌薬抵抗性に及ぼす影響 (2015)
  • Author(s): 村上 圭史
  • Journal Title: 緑膿菌感染症研究会講演記録 Volume: 49 Pages: 67-68
• [Presentation] 付着菌およびバイオフィルムの抗菌薬抵抗性とそのメカニズム (2016)
  • Author(s): 村上 圭史
  • Organizer: 第89回日本細菌学会総会
  • Place of Presentation: 大阪国際交流センター（大阪府大阪市）
  • Year and Date: 2016-03-23
• [Presentation] クラリスロマイシンによる緑膿菌c-di-GMPの誘導 (2016)
  • Author(s): 村上 圭史
  • Organizer: 第50回緑膿菌感染症研究会
  • Place of Presentation: ヒルトン東京お台場（東京都港区）
  • Year and Date: 2016-02-04
• [Presentation] 緑膿菌psl遺伝子が抗菌薬抵抗に及ぼす影響 (2015)
  • Author(s): 村上 圭史
  • Organizer: 第63回日本化学療法学会西日本支部総会
  • Place of Presentation: 奈良春日野国際フォーラム（奈良県奈良市）
  • Year and Date: 2015-10-15
• [Presentation] 新規化合物が薬剤耐性緑膿菌に対する殺菌効果に及ぼす影響 (2015)
  • Author(s): 村上 圭史
  • Organizer: 第63回日本化学療法学会総会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-06-04