Search for circumventors of arbekacin resistance in MRSA produced by microorganisms

2011 Fiscal Year Final Research Report

• Project/Area Number: 21580129
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bioproduction chemistry/Bioorganic chemistry
• Research Institution: Kitasato University
• Principal Investigator: SHIOMI Kazuro 北里大学, 大学院・感染制御科学府, 教授 (40235502)
• Co-Investigator(Renkei-kenkyūsha): TAKAHASHI Yoko 北里大学, 大学院・感染制御科学府, 教授 (80197186) ; MASUMA Rokuro 北里大学, 大学院・感染制御科学府, 准教授 (90219353) ; HANAKI Hideaki 北里大学, 北里生命科学研究所, 室長 (60286747) ; IWATSUKI Masato 北里大学, 北里生命科学研究所, 上級研究員 (70353464)
• Project Period (FY): 2009 – 2011
• Keywords: 薬剤耐性克服 / MRSA / 抗生物質 / アルベカシン / 天然物化学

Research Abstract

Arbekacin is used for MRSA, multi-drug resistant bacteria. However, arbekacin resistant MRSA emerged. It becomes resistant by possessing a bifunctional enzyme that modifies arbekacin by phosphorylation or acetylation. We found aranorosin and biverlactones as circumventors of arbekacin resistance in MRSA. Arbekacin with a combination of those compounds inhibits the growth of arbekacin resistant MRSA.

Research Products

• [Journal Article] Biverlactones A-D, new circumventors of arbekacin resistance in MRSA, produced by Penicillium sp. FKI-4429 (2011)
  • Author(s): M. Iwatsuki, T. Ishimori, T. Yamamoto, K. Takata, M. Mori, K. Nonaka, R. Masuma, Y. Hayakawa, H. Hanaki, K. Shiomi, S. Omura
  • Journal Title: Tetrahedron Volume: Vol.67, No.35 Pages: 6644-6648
  • Peer Reviewed
• [Journal Article] A small-molecule inhibitor of the bacterial type III secretion system protects against in vivo infection with Citrobacter rodentium (2011)
  • Author(s): K. Kimura, M. Iwatsuki, T. Nagai, A. Matsumoto, Y. Takahashi, K. Shiomi, S. Omura, A. Abe
  • Journal Title: J. Antibiot Volume: Vol.64, No.2 Pages: 197-203
  • Peer Reviewed
• [Journal Article] Identification of the active component that induces vancomycin resistance in MRSA (2010)
  • Author(s): S. Ikeda, H. Hanaki, C. Yanagisawa, Y. Ikeda-Dantsuji, H. Matsui, M. Iwatsuki, K. Shiomi, T. Nakae, K. Sunakawa, S. Omura
  • Journal Title: J. Antibiot Volume: Vol.63, No.9 Pages: 533-538
  • Peer Reviewed
• [Journal Article] A quinol peroxidase inhibitor prevents secretion of a leukotoxin from Aggregatibacer actinomycetemcomitans (2010)
  • Author(s): E. Takashima, H. Yamada, A. Yajima, K. Shiomi, S. Omura, K. Kiyoshi
  • Journal Title: J. Periodont. Res Volume: Vol.45, No.1 Pages: 123-128
  • Peer Reviewed
• [Journal Article] Aranorosin circumvents arbekacin-resistance in MRSA by inhibiting the bifunctional enzyme AAC(6')/APH(2")
  • Author(s): T. Suga, T. Ishii, M. Iwatsuki, T. Yamamoto, K. Nonaka, R. Masuma, H. Matsui, H. Hanaki, S. Omura, K. Shiomi
  • Journal Title: J. Antibiot
  • DOI: doi:10.1038/ja.2012.53
  • Peer Reviewed
• [Presentation] 微生物代謝産物からのMRSAに対するアルベカシン耐性克服物質の探索 (2012)
  • Author(s): 須賀拓弥, 石井貴広, 岩月正人, 山本剛, 野中健一, 松本厚子, 増間碌郎, 高橋洋子, 花木秀明, 大村智, 塩見和朗
  • Organizer: 日本農芸化学会2012年度大会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-23
• [Presentation] 新しいターゲットをもつ抗生物質の探索 (2011)
  • Author(s): 塩見和朗
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
  • Year and Date: 2011-03-31
• [Presentation] アルベカシン耐性MRSAの耐性克服物質の探索 (2011)
  • Author(s): 高田恵子, 岩月正人, 山本剛, 石森敏也, 野中健一, 増間碌郎, 松井秀仁, 花木秀明, 早川洋一, 大村智, 塩見和朗
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
  • Year and Date: 2011-03-31
• [Presentation] Bioactive metabolites from tropical microorganisms (2010)
  • Author(s): K. Shiomi, R. Masuma, S. Omura
  • Organizer: 2010 Chinese Academy of Engineering Forum in Frontiers of Medical Sciences
  • Place of Presentation: 中国・広州
  • Year and Date: 2010-12-04
• [Presentation] アルベカシン耐性MRSAの耐性克服物質の探索 (2010)
  • Author(s): 石森敏也, 岩月正人, 山本剛, 高田恵子, 野中健一, 増間碌郎, 松井秀仁, 花木秀明, 早川洋一, 塩見和朗, 大村智
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-28
• [Book] 化学療法学.病原微生物・がんと戦う- (2009)
  • Author(s): 塩見和朗
  • Total Pages: 315
  • Publisher: 南江堂
• [Book] Physiology and Genetics : Selected Basic and Applied Aspects (2009)
  • Author(s): R. Masuma, K. Shiomi, S. Omura
  • Total Pages: 410
  • Publisher: Springer-Verlag
• [Remarks] 科学新聞(2012年3月23日)
• [Remarks] アルベカシン耐性MRSAの耐性克服物質微生物代謝産物から発見
• [Remarks] 日経産業新聞(2012年4月6日)
• [Remarks] 院内感染の原因MRSA抗生物質に再び薬効北里大、カビの一種が一役
• [Patent(Industrial Property Rights)] Novel FKI-4429 substance and method for producing same (2011)
  • Inventor(s): S. Omura, M. Iwatsuki, R. Masuma, K. Nonaka, T. Yamamoto, H. Hanaki, K. Shiomi
  • Industrial Property Rights Holder: The Kitasato Institute
  • Industrial Property Number: 特許、WO2011/111738
  • Filing Date: 2011-03-09
  • Overseas
• [Patent(Industrial Property Rights)] 新規FKI-4429物質およびその製造方法 (2010)
  • Inventor(s): 大村智,岩月正人,増間碌郎,野中健一,山本剛,花木秀明,塩見和朗
  • Industrial Property Rights Holder: (学)北里研究所
  • Industrial Property Number: 特許、特願2010-52838
  • Filing Date: 2010-03-10