侵入因子の制御遺伝子を破壊した動物モデルによる白癬菌病原性発現過程の解析

2009 年度 研究成果報告書

• 研究課題/領域番号: 19590457
• 研究種目: 基盤研究(C)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 細菌学(含真菌学)
• 研究機関: 帝京大学
• 研究代表者: 槇村 浩一 帝京大学, 医学部, 准教授 (00266347)
• 研究分担者: 山田 剛 帝京大学, 医真菌研究センター, 講師 (80424331) ; 西山 彌生 帝京大学, 医療技術学部, 教授 (10082231)
• 研究期間 (年度): 2007 – 2009
• キーワード: 病原性 / 白癬菌 / 動物モデル / 形質転換 / 病原因子 / 遺伝子破壊 / 遺伝子診断

研究概要

白癬菌の主に侵入因子制御遺伝子破壊株と同野性株を用いた白癬動物モデル実験により、白癬の病原因子候補となっている侵入因子と感染成立とに関わる機序の解明を可能にする以下の研究ツールを研究・開発した。本研究によって、国民病でもある白癬の病態、並びに「侵入因子の制御遺伝子を破壊した動物モデルによる白癬菌病原性発現過程を解析」するための基本的ツールが整備された。

研究成果

• [雑誌論文] Rapid identification of Prototheca zopfii by nested polymerase chain reaction based on the nuclear small subunit ribosomal DNA. (2009)
  • 著者名/発表者名: Onozaki M, Makimura K, Hasagawa A
  • 雑誌名: Journal of Dermatological Science 54(1) ページ: 56-59
• [雑誌論文] In vitro antifungal activities of luliconazole, a new topical imidazole (2009)
  • 著者名/発表者名: Koga H, Nanjoh Y, Makimura K, Tsuboi R
  • 雑誌名: Medical Mycology 47(6) ページ: 640-647
• [雑誌論文] Agrobacterium tumefaciens-mediated transformation of the dermatophyte, Trichophyton mentagrophytes: an efficient tool for gene transfer. (2009)
  • 著者名/発表者名: Yamada T, Makimura K, Satoh K, Umeda Y, Ishihara Y, Abe S
  • 雑誌名: Medical Mycology 47(5 ページ: 485-494
• [雑誌論文] Evaluation of a new rapid molecular diagnostic system for Plasmodium falciparum combined with DNA filter paper, loop-mediated isothermal amplification (LAMP) and melting curve analysis (2009)
  • 著者名/発表者名: Yamamura M, Makimura K, Ota Y
  • 雑誌名: Japanese Journal of Infectious Diseases 62(1) ページ: 20-25
• [雑誌論文] Direct Colony PCR of Several Medically Important Fungi using AmpdirectR Plus. (2009)
  • 著者名/発表者名: AlShahni MM, Makimura K, Yamada T, Satoh K, Ishihara Y, Takatori K, Sawada T
  • 雑誌名: Japanese Journal of Infectious Diseases 62(2) ページ: 164-167
• [雑誌論文] Comparative study of direct PCR, microscopic examination, and culture-based morphological methods for detection and identification of dermatophytes in nail and skin samples (2009)
  • 著者名/発表者名: Uchida T, Makimura K, Ishihara K, Goto H, Tajiri Y, Okuma M, Fujisaki R, Uchida K, Abe S, Iijima M
  • 雑誌名: ournal of Dermatology 36(4) ページ: 202-208
• [雑誌論文] Is Bjerkandera adusta important to fungus-associated chronic cough as an allergen? (2009)
  • 著者名/発表者名: Ogawa H, Fujimura M, Takeuchi Y, Makimura K
  • 雑誌名: Eight cases report. Journal of Asthma 46(8) ページ: 849-55
• [雑誌論文] Efficacy of itraconazole in the treatment of patients with chronic cough whose sputa yield basidiomycetous fungi (2009)
  • 著者名/発表者名: Ogawa H, Fujimura M, Takeuchi Y, Makimura K
  • 雑誌名: fungus-associated chronic cough (FACC) Journal of Asthma 46(4) ページ: 407-12
• [雑誌論文] Serum Galactomannan Negative Disseminated Aspergillosis In An Intensive Care Unit (2009)
  • 著者名/発表者名: Saito T, Shime N, ItohK, Fujita N, Saito Y, Shinozaki M, Shibuya K, Makimura K, Hashimoto S
  • 雑誌名: A Case Report. Infection (in press)
• [雑誌論文] Molecular detection of dermatophytes and nondermatophytes in onychomycosis by nested PCR based on 28S ribosomal RNA gene sequences. (2009)
  • 著者名/発表者名: Ebihara M, Makimura K, Sato K, Abe S,, Tsuboi R
  • 雑誌名: British Journal of Dermatology 161(5) ページ: 1038-1044
• [雑誌論文] Quantitative analysis of the cutaneous Malassezia microbiota in 770 healthy Japanese by age and gender using a real-time PCR assay (2009)
  • 著者名/発表者名: Sugita T, Suzuki M, Goto S, Nishikawa A, Hiruma M, Yamazaki T, Makimura K
  • 雑誌名: Medical Mycology May 21 ページ: 1-5
• [雑誌論文] The importance of basidiomycetous fungi cultured from sputum of chronic idiopathic cough (2009)
  • 著者名/発表者名: Ogawa H, Fujimura M, Takeuchi Y, Makimura K
  • 雑誌名: Respiratory Medicine 103(10) ページ: 492-7
• [雑誌論文] Polymerase chain reaction assay for specific identification of Candida guilliermondii (Pichia guilliermondii) (2009)
  • 著者名/発表者名: Yamamura M, Makimura K, Fujisaki R, Satoh K, Kawakami S, Nishiya H, Ota Y.
  • 雑誌名: J Infect Chemother. 15(4) ページ: 214-8
• [雑誌論文] Prototheca cutis sp. nov., a newly discovered pathogen of protothecosis isolated from inflamed human skin. (2009)
  • 著者名/発表者名: Satoh K, Ooe K, Nagayama H, Makimura K.
  • 雑誌名: Int J Syst Evol Microbiol. (in press)
• [雑誌論文] Enhanced gene replacements in Ku80 disruption mutants of the dermatophyte, Trichophyton mentagrophytes. (2009)
  • 著者名/発表者名: Yamada T, Makimura K, Hisajima T, Ishihara Y, Umeda Y, Abe S.
  • 雑誌名: FEMS Microbiol Lett. 298(2) ページ: 208-17
• [雑誌論文] Isolation and identification of Rhizomucor pusillus from pleural zygomycosis in an immunocompetent patient. (2009)
  • 著者名/発表者名: Kimura M, Udagawa SI, Makimura K, Satoh K, Toyazaki N, Ito H.
  • 雑誌名: Medical Mycology 47(8) ページ: 869-873
• [雑誌論文] 26S rDNA-based phylogenetic investigation of Japanese cattle-associated Prototheca zopfii isolates. (2009)
  • 著者名/発表者名: Kishimoto Y, Kano R, Maruyama H, Onozaki M, Makimura K, Ito T, Matsubara K, Hasegawa A, Kamata H.
  • 雑誌名: The Journal of Veterinary Medical Science (in press)
• [雑誌論文] Nourseothricin acetyltransferase: a new dominant selectable marker for the dermatophyte Trichophyton mentagrophytes. (2009)
  • 著者名/発表者名: Alshahni M, Makimura K, Yamada T, Takatori K, Sawada T.
  • 雑誌名: Medical Mycology (in press)
• [雑誌論文] Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital. (2009)
  • 著者名/発表者名: Satoh K, Makimura K, Hasumi Y, Nishiyama Y, Uchida K, Yamaguchi H.
  • 雑誌名: Microbiology and Immunology 53(1) ページ: 41-4
• [雑誌論文] Human External Ear Canal as the Specific Reservoir of Malassezia slooffiae (2009)
  • 著者名/発表者名: Kaneko T, Shiota R, Shibuya S, Watanabe S, Umeda Y, Takeshita K, Yamamoto M, Nishioka K, Makimura K
  • 雑誌名: Medical Mycology (in press)
• [雑誌論文] Typing of Aspergillus fumigatus and Aspergillus niger Strains by Random Amplification of Polymorphic DNA Analysis Using a Six Primer Set. (2009)
  • 著者名/発表者名: Mirhendi H, Moazeni M, Nikaeen M, Makimura K.
  • 雑誌名: Shiraz E-Medical Journal 10(4) ページ: 190-200
• [雑誌論文] Development of loop-mediated isothermal amplification method for diagnosing Pneumocystis pneumonia. (2008)
  • 著者名/発表者名: Uemura N, Makimura K, Onozaki M, Otsuka Y, Shibuya Y, Yazaki H, Kikuchi Y, Abe S, Kudoh S
  • 雑誌名: Journal of Medical Microbiology 57(1) ページ: 50-7
• [雑誌論文] Genetic transformation of the dermatophyte, Trichophyton mentagrophytes, based on the use of G418 resistance as a dominant selectable marker. (2008)
  • 著者名/発表者名: Yamada T, Makimura K, Hisajima T, Ito M, Umeda Y, Abe S
  • 雑誌名: Journal of Dermatological Science 49(1) ページ: 53-61
• [雑誌論文] Exotic myiasis caused by 19 larvae of Cordylobia anthropophaga in Namibia and identified using molecular methods in Japan. (2008)
  • 著者名/発表者名: Fijisaki R, Makimura K, Hayashi T, Yamamura M, Yamaoka T, Shiraishi K, Ishihbashi S, Kawakami S, Kurihara T, Nishihya H
  • 雑誌名: Transactions of the Royal Society of Tropical Medicine and Hygiene 102(6) ページ: 599-601
• [雑誌論文] Prototheca zopfii genotypes isolated from cow barns and bovine mastitis in Japan. (2008)
  • 著者名/発表者名: Osumi T, Kishimoto Y, Kano R, Maruyama H, Onozaki M, Makimura K, Ito T, Matsubara K, Hasegawa A
  • 雑誌名: Veterinary Microbiolgy 131(3-4) ページ: 419-423
• [雑誌論文] A new genotype of Arthroderma benhamiae. (2008)
  • 著者名/発表者名: Kano R, Sano A, Makimura K, Watanabe S, Nishimura K, Yamaguchi H, Hasegawa A
  • 雑誌名: Medical Mycology 46(7) ページ: 739-744
• [雑誌論文] Protective effects of farnesol against oral candidiasis in mice. (2008)
  • 著者名/発表者名: Hisajima T, Maruyama N, Tanabe Y, Ishibashi H, Yamada T, Makimura K, Nishiyama Y, Funakoshi K, Oshima H, Abe S
  • 雑誌名: Microbiology and Immunology 52(7) ページ: 327-33
• [雑誌論文] Comparative evaluation of Trichosporon asahii susceptibility using ASTY colorimetric microdilution and CLSI M27-A2 broth microdilution reference methods. (2008)
  • 著者名/発表者名: Kalkanci A, Mekha N, Poonwan N, Makimura K, Sugita T
  • 雑誌名: Microbiol Immunol 52(9) ページ: 435-439
• [雑誌論文] Sporobolomyces koalae sp. nov., a novel basidiomycetous yeast isolated from the nasal smear of Queensland koalas kept in a Japanese zoological park (2008)
  • 著者名/発表者名: Satoh K, Makimura K
  • 雑誌名: International Journal of Systematic and Evolutionary Microbiology 58(Pt12) ページ: 2983-2986
• [雑誌論文] Is Histoplasma capsulatum a native inhabitant of Japan? (2008)
  • 著者名/発表者名: Kikuchi K, Sugita T, Makimura K, Urata K, Someya T, Sasaki T, Kamei K, Niimi M, Hiramatsu K, Uehara Y
  • 雑誌名: Microbiology and Immunology 52(9) ページ: 455-459
• [雑誌論文] A new genotype of Arthroderma benhamiae. (2008)
  • 著者名/発表者名: Kano R, Sano A, Makimura K, Watanabe S, Nishimura K, Yamaguchi H, Hasegawa A.
  • 雑誌名: Medical Mycology Nov 46(7) ページ: 739-44
• [雑誌論文] The effect of dermatophytes on cytokine production by human keratinocytes. (2007)
  • 著者名/発表者名: Tani K, Adachi M, Nakamura Y, Kano R, Makimura K, Hasegawa A, Kanda N, Watanabe S.
  • 雑誌名: Arch Dermatol Res 299(8) ページ: 381-7
• [雑誌論文] Identification of pathogenic Aspergillus species by a PCR-restriction enzyme method. (2007)
  • 著者名/発表者名: Mirhendi H, Diba K, Kordbacheh P, Jalalizand N, Makimura K
  • 雑誌名: Journal of Medical Microbiology 56(11) ページ: 1568-70
• [雑誌論文] Revised culture based identification system for Malassezia Journal of Clinical Microbiology (2007)
  • 著者名/発表者名: Kaneko T, Makimura K, Abe M, Shiota R, Nakamura Y, Kano R, Hasegawa A, Sugita T, Shibuya S, Watanabe S, Yamaguchi H, Abe S, Okamura N
  • 雑誌名: 45(11) ページ: 3737-42
• [学会発表] Development of Analyzing System for Microbial Flora on board Space Station and Astronauts. (2007)
  • 著者名/発表者名: Koichi MAKIMURA, Kazuo SATOH, Tsuyoshi YAMADA, Yayoi NISHIYAMA, Shigeru ABE, Yuuji TSUKII, Takashi SUGITA, Kosuke TAKATORI, Yoshimi BENNO, Takashi YAMAZAKI
  • 学会等名: The 5th ISLSWG International Workshop on Space Microbiology
  • 発表場所: Tokyo
  • 年月日: 20070919-20070921
• [図書] 真菌症の診断と治療ハリソン内科学第3版Part7感染症Section 16真菌および微細藻類感染症 (2009)
  • 著者名/発表者名: 槇村浩一
  • 総ページ数: 1304-1306
• [備考] 帝京大学医真菌研究センターウェブサイト
  • URL: http://timm.main.teikyo-u.ac.jp
• [備考] 病原真菌データーベース
  • URL: http://www.pfdb.net/
• [産業財産権] 遺伝子破壊白癬菌 (2008)
  • 発明者名: 槇村浩一、山田剛、安部茂
  • 権利者名: 槇村浩一、山田剛、安部茂
  • 産業財産権番号: 特願2008-11432
  • 出願年月日: 2008-04-22
• [産業財産権] 爪真菌症の診断法 (2008)
  • 発明者名: 坪井良治、槇村浩一、海老原睦仁
  • 権利者名: 坪井良治、槇村浩一、海老原睦仁
  • 産業財産権番号: 特願2008-67605
  • 出願年月日: 2008-03-27