Study of the reaction between beta-lactam antibiotids and thiol compounds

• Project/Area Number: 15H06509
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Bacteriology (including mycology)
• Research Institution: Kumamoto University
• Principal Investigator: Ono Katsuhiko 熊本大学, 大学院生命科学研究部(医), 助教 (80573592)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: βラクタム系抗生物質 / システイン / チオール化合物 / βラクタム系抗生物

Outline of Final Research Achievements

Recently we found that beta-lactam antibiotics is inactivated by reaction with thiol compounds such as cysteine. On the basis of LC-MSMS and NMR analysis, it was shown that beta-lactam antibiotics and cysteine formed one to one adduct. E.coli fliY mutant, which is loss of cysteine/cystien shuttle system, showed high-sensitive to beta-lactam antibiotics and produced less cysteine-beta lactic antibiotics adduct compared with wild type strain. These results suggest that bacterial cysteine might contribute to antibiotics resistance via formation of cysteine-beta-lactam antibiotics adduct in periplasmic space.

Research Products

• [Journal Article] 細菌の硫化水素・RSSの代謝シグナル制御． (2019)
  • Author(s): 津々木博康、小野勝彦、澤 智裕．
  • Journal Title: 細胞工学 Volume: 34 Pages: 92-395
• [Journal Article] Synthesis of L-cysteine derivatives containing stable sulfur isotopes and application of this synthesis to reactive sulfur metabolome (2017)
  • Author(s): Ono K, Jung M, Zhang T, Tsutsuki H, Sezaki H, Ihara H, Wei FY, Tomizawa K, Akaike T, Sawa T.
  • Journal Title: Free Radic Biol Med Volume: 106 Pages: 69-79
  • DOI: 10.1016/j.freeradbiomed.2017.02.023
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Silver nanoparticles as potential antibiofilm agents against human pathogenic bacteria (2017)
  • Author(s): Kyaw K, Harada A, Ichimaru H, Kawagoe T, Yahiro K, Morimura S, Ono K, Tsutsuki H, Sawa T, Niidome T.
  • Journal Title: Chem Lett Volume: 46 Issue: 4 Pages: 594-596
  • DOI: 10.1246/cl.161198
  • NAID: 130005549076
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Synthesis and Characterization of 8-Nitroguanosine 3′,5′-Cyclic Monophosphorothioate Rp-Isomer as a Potent Inhibitor of Protein Kinase G1α (2017)
  • Author(s): Ahmed KA, Zhang T, Ono K, Tsutsuki H, Ida T, Akashi S, Miyata K, Oike Y, Akaike T, Sawa T.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 40 Issue: 3 Pages: 365-374
  • DOI: 10.1248/bpb.b16-00880
  • NAID: 130005398514
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Protein polysulfidation-dependent persulfide dioxygenase activity of ethylmalonic encephalopathy protein 1 (2016)
  • Author(s): Jung M, Kasamatsu S, Matsunaga T, Akashi S, Ono K, Nishimura A, Morita M, Abdul Hamid H, Fujii S, Kitamura H, Sawa T, Ida T, Motohashi H, Akaike T.
  • Journal Title: Biochem Biophys Res Commun Volume: 480 Issue: 2 Pages: 180-186
  • DOI: 10.1016/j.bbrc.2016.10.022
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Persistent activation of cGMP-dependent protein kinase by a nitrated cyclic nucleotide via site specific protein S-guanylation (2016)
  • Author(s): Akashi S, Ahmed KA, Sawa T, Ono K, Tsutsuki H, Burgoyne JR, Ida T, Horio E, Prysyazhna O, Oike Y, Rahaman MM, Eaton P, Fujii S, Akaike T.
  • Journal Title: Biochemistry Volume: 55 Issue: 5 Pages: 751-761
  • DOI: 10.1021/acs.biochem.5b00774
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The Chemical Biology of Hydropersulfides (RSSH): Chemical Stability, Reactivity and Redox Roles. (2015)
  • Author(s): Saund, S. S., Sosa, V., Henriquez, S., Nguyen, Q. N. N., Soeda, S., Bianco, C. L., Millikin, R., White, C., Le, H., Ono, K., Tantillo, D. J., Kumagai, Y., Akaike, T., Lin, J., Fukuto, J. M.
  • Journal Title: Arch. Biochem. Biophys. Volume: 588 Pages: 15-24
  • DOI: 10.1016/j.abb.2015.10.016
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] チオール基とβラクタム系抗生物質の反応性に基づく新規βラクタム－タンパク質付加体形性の同定とその生物学的意義の解明 (2017)
  • Author(s): 小野勝彦、津々木博康、張田力、瀬崎浩史、赤池孝章、澤智裕
  • Organizer: 第９０回日本細菌学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-19
• [Presentation] Rp-ニトロcGMPによるS-グアニル化を介したプロテインキナーゼG（PKG）の活性阻害 (2016)
  • Author(s): 小野 勝彦、Ahtesham Ahmed Khandarker、津々木 博康、張 田力、井田 智章、宮田 敬士、尾池 雄一、赤池 孝章、澤 智裕
  • Organizer: 第69回日本酸化ストレス学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2016-08-30
• [Presentation] 細菌におけるシステインパースルフィド関連分子の生成動態 (2016)
  • Author(s): 澤 智裕, 張 田力, 小野勝彦, 津々木博康, 赤池孝章
  • 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（大阪市）
  • Year and Date: 2016-03-23
• [Presentation] 腸管出血性大腸菌毒素 Subtilase cytotoxin によるインフラマソーム抑制機構の解析 (2016)
  • Author(s): 津々木博康, Thianli Zhang, 小野勝彦, 八尋錦之助, 野田広俊, 澤 智裕
  • 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（大阪市）
  • Year and Date: 2016-03-23
• [Presentation] チオール化合物とβラクタム系抗生物質との反応による付加体形成：抗菌作用への影響と標的タンパク質の同定 (2016)
  • Author(s): 小野勝彦, 津々木博康, 赤池孝章, 澤 智裕
  • 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（大阪市）
  • Year and Date: 2016-03-23
• [Presentation] 大腸菌における蛋白質S-グアニル化の制御因子と標的タンパク質の同定 (2015)
  • Author(s): 津々木博康、小野勝彦、井田智章、張 田力、居原 秀、赤池孝章、澤 智裕
  • Organizer: 第68回日本細菌学会九州支部総会第52回日本ウイルス学会九州支部総会
  • Place of Presentation: 別府コンベンションプラザ・ビーコンプラザ（大分県別府市）
  • Year and Date: 2015-09-04
• [Presentation] 細菌におけるシステインパースルフィドおよび関連分子の生成動態 (2015)
  • Author(s): 小野勝彦、津々木博康、張 田力、赤池孝章、澤 智裕
  • Organizer: 第68回日本細菌学会九州支部総会第52回日本ウイルス学会九州支部総会
  • Place of Presentation: 別府コンベンションプラザ・ビーコンプラザ（大分県別府市）
  • Year and Date: 2015-09-04
• [Remarks] 熊本大学微生物学分野
  • URL: http://kumadai-bisei.com
• [Remarks] 熊本大学微生物学分野ホームページ
  • URL: http://kumadai-bisei.com/