Role of mitophagy of Candida glabrata in pathogenicity.

• Project/Area Number: 26860296
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Bacteriology (including mycology)
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Minoru Nagi 国立感染症研究所, 真菌部, 研究員 (60711687)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: マイトファジー / ATG32 / オートファジー / 病原真菌 / 酵母 / ミトコンドリア / Candida glabrata / 病原性 / カンジダ / 鉄欠乏 / Candida

Outline of Final Research Achievements

The Screening of mitophagy activation conditions indicated that mitophagy was induced in Candida glabrata cells under iron-poor conditions, and that the disruption of ATG32, which is responsible for mitophagy in Saccharomyces cerevisiae, blocked mitophagy in C. glabrata. Unexpectedly, the mitophagy-deficient mutant of C. glabrata (atg32Δ) exhibited decreased longevity under iron-depleted conditions. The mitochondrial membrane potential in atg32Δ cells was significantly lower than that in wild-type (WT) cells under iron-depleted conditions. In a mouse model of disseminated infection, the atg32Δ strain resulted in significantly decreased kidney and spleen fungal burdens compared with WT strain. These results indicate that mitophagy in C. glabrata occurs in an iron-poor host tissue environment, and it may contribute to the longevity of cells through mitochondrial quality control, and to their pathogenesis.

Research Products

• [Journal Article] Iron-depletion promotes mitophagy to maintain mitochondrial integrity in pathogenic yeast Candida glabrata. (2016)
  • Author(s): Nagi M, Tanabe K, Nakayama H, Ueno K, Yamagoe S, Umeyama T, Ohno H, Miyazaki Y.
  • Journal Title: Autophagy Volume: 12 Issue: 8 Pages: 1259-1271
  • DOI: 10.1080/15548627.2016.1183080
  • Peer Reviewed / Open Access
• [Journal Article] Interferon-γ promotes phagocytosis of Cryptococcus neoformans but not Cryptococcus gattii by murine macrophages (2015)
  • Author(s): Ikeda-Dantsuji Y, Ohno H, Tanabe K, Umeyama T, Ueno K, Nagi M, Yamagoe S, Kinjo Y, Miyazaki Y
  • Journal Title: J Infect Chemother Volume: 21 Issue: 12 Pages: 831-836
  • DOI: 10.1016/j.jiac.2015.08.001
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The mannoprotein TIR3 (CAGL0C03872g) is required for sterol uptake in Candida glabrata. Biochim Biophys Acta. (2015)
  • Author(s): 1.Inukai T, Nagi M, Morita A, Tanabe K, Aoyama T, Miyazaki Y, Bard M, Nakayama H
  • Journal Title: Biochim Biophys Acta. Volume: 1851 Issue: 2 Pages: 141-151
  • DOI: 10.1016/j.bbalip.2014.11.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Genome-wide survey of transcriptional initiation in the pathogenic fungus, Candida glabrata (2014)
  • Author(s): Toshihiro Aoyama, Hironobu Nakayama, Keigo Ueno K, Tatsuya Inukai T, Koichi Tanabe, Minoru Nagi, Martin M. Bard Hiroji Chibana
  • Journal Title: Genes Cells Volume: (in press) Issue: 6 Pages: 478-503
  • DOI: 10.1111/gtc.12147
  • Peer Reviewed
• [Presentation] Candida glabrataのミトコンドリア選択的オートファジーと病原性 (2017)
  • Author(s): 名木 稔、田辺公一、上野圭吾、中山浩伸、中村茂樹、梅山 隆、山越 智、宮﨑義継
  • Organizer: 第90回日本細菌学会総会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2017-03-19
  • Invited
• [Presentation] Candida glabrata のミトコンドリア選択的オートファジー（マイトファジー）が病原性に及ぼす影響 (2016)
  • Author(s): 名木 稔、田辺公一、中山浩伸、上野圭吾、犬飼達也、中村茂樹、梅山 隆、山越 智、大野秀明、宮﨑義継
  • Organizer: 第60回日本医真菌学会総会・学術集会
  • Place of Presentation: 東京都立産業貿易センター台東館
  • Year and Date: 2016-10-01
• [Presentation] Candida glabrataのミトコンドリア選択的オートファジーと病原性 (2016)
  • Author(s): 名木 稔、田辺公一、中山浩伸、上野圭吾、犬飼達也、中村茂樹、梅山 隆、山越 智、大野秀明、宮﨑義継
  • Organizer: 第60回日本医真菌学会総会・学術集会
  • Place of Presentation: 東京都立産業貿易センター台東館
  • Year and Date: 2016-10-01
  • Invited
• [Presentation] Iron-depletion promotes mitophagy in pathogenic yeast Candida glabrata (2016)
  • Author(s): Minoru Nagi, Koichi Tanabe, Hironobu Nakayama, Keigo Ueno, Satoshi Yamagoe, Takashi Umeyama, Hideaki Ohno, Yoshitsugu Miyazaki
  • Organizer: 14th International Congress on Yeasts
  • Place of Presentation: 淡路夢舞台国際会議場
  • Year and Date: 2016-09-11
  • Int'l Joint Research
• [Presentation] Candida glabrataの細胞外ステロール取り込みが抗真菌薬感受性、病原性に及ぼす影響 (2016)
  • Author(s): 名木 稔、田辺公一、犬飼達也、上野圭吾、中村茂樹、梅山 隆 、山越 智、大野秀明、宮崎義継
  • Organizer: 第64回 日本化学療法学会総会
  • Place of Presentation: 神戸国際会議場・神戸ポートピアホテル
  • Year and Date: 2016-06-09
• [Presentation] 鉄欠乏条件において誘導される Candida glabrata のミトコンドリア選択的オートファジー（マイト ファジー）が病原性に及ぼす影響 (2016)
  • Author(s): 名木 稔，田辺公一，中村茂樹，梅山 隆，山越 智, 大野秀明，宮﨑義継
  • Organizer: 第90回日本感染症学会総会・学術講演会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2016-04-15
• [Presentation] カンジダ属の薬剤耐性の現状と課題 (2015)
  • Author(s): 名木 稔, 田辺公一, 中山浩伸, 犬飼達也, 梅山 隆, 山越 智, 中村茂樹, 大野秀明, 宮﨑義継
  • Organizer: 第59回日本医真菌学会総会・学術集会
  • Place of Presentation: ホテル さっぽろ芸文館
  • Year and Date: 2015-10-10
  • Invited
• [Presentation] Candida glabrataの細胞外ステロール取り込みが抗真菌薬感受性、病原性に及ぼす影響 (2015)
  • Author(s): 名木 稔, 田辺公一, 犬飼達也, 梅山 隆, 山越 智,大野秀明, 宮﨑義継
  • Organizer: 第59回日本医真菌学会総会・学術集会
  • Place of Presentation: ホテル さっぽろ芸文館
  • Year and Date: 2015-10-10
• [Presentation] Candida glabrataの細胞外ステロール取り込みが抗真菌薬感受性、病原性に及ぼす影響 (2015)
  • Author(s): 名木 稔, 田辺公一, 犬飼達也, 梅山 隆, 山越 智,大野秀明, 宮﨑義継
  • Organizer: 第63回日本化学療法学会総会
  • Place of Presentation: 京王プラザホテル新宿
  • Year and Date: 2015-06-06
• [Presentation] 真菌の薬剤耐性の現状と課題 (2014)
  • Author(s): 名木 稔、田辺公一、石野敬子、梅山 隆、山越 智、大野秀明、宮﨑義継
  • Organizer: 第63回日本感染症学会東日本地方会学術集会
  • Place of Presentation: 東京ドームホテル
  • Year and Date: 2014-10-29
  • Invited