Whole genome sequencing of pathogenic microorganisms causing septic shock

• Project/Area Number: 16H05496
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Chiba University
• Principal Investigator: Sekine Akihiro 千葉大学, 予防医学センター, 教授 (30425631)
• Co-Investigator(Kenkyū-buntansha): 中田 孝明 千葉大学, 大学院医学研究院, 講師 (20375794)
• Research Collaborator: Mashimo Yoichi ; Mitsunaga Toshiya ; Yamashita Taiki ; Takahashi Nozomi ; Takaya Akiko ; Murata Syota
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000); Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
• Keywords: 敗血症 / 病原性微生物 / 全ゲノム / PacBioRSⅡ/Sequel / 変異 / データベ―ス / 全ゲノムシーケンス / 全ゲノム解析 / long read型シーケンサ― / 敗血症ショック / PacBioRSⅡ / 全ゲノム配列決定

Outline of Final Research Achievements

The whole genome sequence was determined by PacBioRSII / Sequel from blood culture bacterial samples of 301 cases of sepsis. Bacterial species are E. coli (136 cases), K. pneumoniae (94), P. aeruginosa (44), K. oxytoca (11), E. cloacae (7), and rare cases, Aeromonas. Spp (3), E. aerogenes (2), R. ornithololytica (1), S. maltophilia (1), S. marcescens (1). The simultaneous detection of E. coli and K. pneumoniae (2) was also observed. All strains were able to determine the entire novel genome, and several structural mutations associated with sepsis were detected from the E. coli K. pneumoniae group. These were made into a database, and it was set as the situation which a critical care worker can read.

Academic Significance and Societal Importance of the Research Achievements

敗血症に発症に関わる多数の病原性微生物全ゲノム配列を取りまとめた情報はない。一方、本研究代表者・研究分担者は敗血症例のヒトGWASデータ約800人の情報も所持し、ヒト感受性ー病原性微生物種・全ゲノム情報を備えたことは、ほぼ原因が不明である宿主・感染の相互作用を理解するための重要な基盤情報となる。すでに、千葉大学の救命救急医療従事者にはデータベースとして共有化を開始し、意見徴集を行った後、将来は、千葉大学外の当該領域関係者とも共有化を図り、敗血症解決への基盤に発展させる予定である。

Research Products

• [Journal Article] Reduction in Gastroesophageal Reflux Disease Symptoms Is Associated with <i>Miso</i> Soup Intake in a Population-Based Cross-Sectional Study: The Nagahama Study (2018)
  • Author(s): MANO Fumika、IKEDA Kaori、SATO Tosiya、NAKAYAMA Takeo、TANAKA Daisuke、JOO Erina、TAKAHASHI Yoshimitsu、KOSUGI Shinji、SEKINE Akihiro、TABARA Yasuharu、MATSUDA Fumihiko、INAGAKI Nobuya、Nagahama Study Group
  • Journal Title: Journal of Nutritional Science and Vitaminology Volume: 64 Issue: 5 Pages: 367-373
  • DOI: 10.3177/jnsv.64.367
  • NAID: 130007501995
  • ISSN: 0301-4800, 1881-7742
  • Year and Date: 2018-10-31
  • Peer Reviewed / Open Access
• [Journal Article] Dietary habits associated with reduced insulin resistance: The Nagahama study. (2018)
  • Author(s): Ikeda K, Sato T, Nakayama T, Tanaka D, Nagashima K, Mano F, Joo E, Fujimoto S, Takahashi Y, Kosugi S, Sekine A, Tabara Y, Matsuda F, Inagaki N; Nagahama Study Group.
  • Journal Title: Diabetes Res Clin Pract. Volume: 141 Pages: 26-34
  • Peer Reviewed / Open Access
• [Journal Article] Evolution of multi-drug resistant HCV clones from pre-existing resistant-associated variants during direct-acting antiviral therapy determined by third-generation sequencing. (2017)
  • Author(s): Takeda H, Ueda Y, Inuzuka T, Yamashita Y, Osaki Y, Nasu A, Umeda M, Takemura R, Seno H, Sekine A, Marusawa H.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 45605-45605
  • DOI: 10.1038/srep45605
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Combined association of clinical and lifestyle factors with non-restorative sleep: The Nagahama Study. (2017)
  • Author(s): Matsumoto T, Tabara Y, Murase K, Takahashi Y, Setoh K, Kawaguchi T, Muro S, Kadotani H, Kosugi S, Sekine A, Yamada R, Nakayama T, Mishima M, Matsuda F, Chin K.
  • Journal Title: PLoS One. Volume: 12 Issue: 3 Pages: e0171849-e0171849
  • DOI: 10.1371/journal.pone.0171849
  • NAID: 120006539727
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Risks and Cough-Aggravating Factors in Prolonged Cough: Epidemiological Observations from the Nagahama Cohort Study. (2017)
  • Author(s): Matsumoto H, Izuhara Y, Niimi A, Tabara Y, Nagasaki T, Kanemitsu Y, Murase K, Oguma T, Ito I, Muro S, Sekine A, Matsuda F, Kosugi S, Nakayama T, Chin K, Mishima M; Nagahama Study Collaboration Group..
  • Journal Title: Ann Am Thorac Soc. Volume: Feb 10. Issue: 5 Pages: 698-705
  • DOI: 10.1513/annalsats.201608-616bc
  • Peer Reviewed / Open Access
• [Journal Article] Hypothalamic AMP-Activated Protein Kinase Regulates Biphasic Insulin Secretion from Pancreatic β Cells during Fasting and in Type 2 Diabetes. (2016)
  • Author(s): Kume S, Kondo M, Maeda S, Nishio Y, Yanagimachi T, Fujita Y, Haneda M, Kondo K, Sekine A, Araki SI, Araki H, Chin-Kanasaki M, Ugi S, Koya D, Kitahara S, Maeda K, Kashiwagi A, Uzu T, Maegawa H.
  • Journal Title: EBioMedicine. Volume: 13 Pages: 168-180
  • DOI: 10.1016/j.ebiom.2016.10.038
  • Peer Reviewed / Open Access
• [Journal Article] Relationship Among Chlamydia and Mycoplasma Pneumoniae Seropositivity, IKZF1 Genotype and Chronic Obstructive Pulmonary Disease in A General Japanese Population: The Nagahama Study. (2016)
  • Author(s): Muro S, Tabara Y, Matsumoto H, Setoh K, Kawaguchi T, Takahashi M, Ito I, Ito Y, Murase K, Terao C, Kosugi S, Yamada R, Sekine A, Nakayama T, Chin K, Mishima M, Matsuda F; Nagahama Study Group.
  • Journal Title: Medicine (Baltimore). Volume: 95(15) Issue: 15 Pages: e3371-e3371
  • DOI: 10.1097/md.0000000000003371
  • Peer Reviewed / Open Access
• [Journal Article] Mouth Breathing, another Risk Factor for Asthma: the Nagahama Study. (2016)
  • Author(s): Yumi I, Matsumoto H, Nagasaki T, Kanemitsu Y, Murase K, Ito I, Oguma T, Muro S, Asai K, Tabara Y, Takahashi K, Bessho K, Sekine A, Kosugi S, Yamada R, Nakayama T, Matsuda F, Niimi A, Chin K, Mishima M; Nagahama Study Group.
  • Journal Title: Allergy Volume: 未定 Issue: 7 Pages: 1031-1036
  • DOI: 10.1111/all.12885
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Chiba study of Mother and Children's Health (C-MACH): cohort study with omics analyses. (2016)
  • Author(s): Sakurai K, Miyaso H, Eguchi A, Matsuno Y, Yamamoto M, Todaka E, Fukuoka H, Hata A, Mori C; Chiba study of Mother and Children's Health Group.
  • Journal Title: BMJ Open Volume: 29 Issue: 1 Pages: e010531-e010531
  • DOI: 10.1136/bmjopen-2015-010531
  • Peer Reviewed / Open Access
• [Journal Article] Synergistic association of elevated serum free fatty acid and glucose levels with large arterial stiffness in a general population: The Nagahama Study (2016)
  • Author(s): Yasuharu Tabara, Yoshimitsu Takahashi, Kazuya Setoh, Takahisa Kawaguchi, Norimoto Gotoh, Chikashi Terao, Ryo Yamada, Shinji Kosugi, Akihiro Sekine, Takeo Nakayama, Fumihiko Matsuda, on behalf of the Nagahama Study group.
  • Journal Title: M E T A B O L I S M C L I N I C A L A N D E X P E R I M E N T A L Volume: 65 Issue: 1 Pages: 66-72
  • DOI: 10.1016/j.metabol.2015.10.011
  • NAID: 120005698009
  • Peer Reviewed / Open Access
• [Presentation] レジストリ研究からみる特発性血栓症患者の特徴 (2019)
  • Author(s): 辻明宏、宮田敏行、関根章博
  • Organizer: 第13回日本血栓止血学会各術標準化委員会シンポジウム
• [Presentation] シーケンス・タイピングを用いた遺伝子診断における精度低下を招く問題点と改善点 (2017)
  • Author(s): 関根章博、山下泰生、北原輝栄、竹村亮、羽田明
  • Organizer: 第24回日本遺伝子診療学会大会
  • Invited
• [Presentation] AIを想定した医療ビックデータの収集解析 (2017)
  • Author(s): 関根章博、山下泰生、竹村亮、真下陽一、井上正宏
  • Organizer: 日本動物実験代替法学会第30回大会
  • Invited
• [Presentation] Third-generation sequencing unveils the evolution of multi-drug resistant hepatitis C virus clones during direct-acting antiviral therapy. (2017)
  • Author(s): Haruhiko Takeda, Yoshihide Ueda, Tadashi Inuzuka, Shigeru Ohtsuru, Hiroshi Seno, Akihiro Sekine and Hiroyuki Marusawa.
  • Organizer: American Association for Study of Liver Diseases (AASLD)
  • Int'l Joint Research
• [Presentation] Serum lipid metabolomics can predict sensitivity to bortezomib treatment in multiple myeloma (2016)
  • Author(s): Masaki Ri, Kazuo Okemoto, Keiko Maekawa, Takashi Ishida, Miki Nakajima, Akihiro Sekine, Ryuzo Ueda, Masahiro Tohkin, Naoki Miyata, Yoshiro Saito, Shinsuke Iida
  • Organizer: 第78回日本血液学会学術集会
  • Place of Presentation: 神奈川横浜市西区パシフィコ横浜
  • Year and Date: 2016-10-13
• [Book] 正確なサンガ法を行うために (2018)
  • Author(s): 関根章博,光永敏哉,真下陽一
  • Total Pages: 322
  • Publisher: 医学のあゆみ
• [Book] PacBioRSⅡを用いたインターフェロンフリー療法無効症例の原因となった変異の検出法 (2018)
  • Author(s): 関根章博,竹田治彦,山下泰生,丸澤宏之
  • Total Pages: 256
  • Publisher: 医学のあゆみ
• [Remarks] 千葉大学予防医学センターホームページ
  • URL: http://cpms.chiba-u.jp/
• [Remarks] Center for preventive medical science, Chiba univ.
  • URL: http://cpns.chiba-u.jp