Investigation of virulence mechanism of Gram-positive bacteria regulated by various RNA binding proteins

• Project/Area Number: 19H03466
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: Okayama University
• Principal Investigator: KAITO Chikara 岡山大学, 医歯薬学域, 教授 (60420238)
• Co-Investigator(Kenkyū-buntansha): 寺尾 豊 新潟大学, 医歯学系, 教授 (50397717) ; 古田 和幸 岡山大学, 医歯薬学域, 准教授 (50644936)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2020: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2019: ¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000)
• Keywords: 酸化ヌクレオチド / カイコプラズマ / RpoB / リファンピシン / エリスロマイシン / 病原性 / 8-oxo-GTP / 酸化ストレス / 病原性因子 / ヌクレオチドピロフォスファターゼ / RNA相互作用因子 / グラム陽性細菌 / 病原性制御

Outline of Research at the Start

本研究の目的は、細菌が宿主環境を認識し、病原因子を発現制御する過程におけるRNA相互作用因子群の役割を明らかにすることである。本課題では、代表者が確立した細菌の病原性評価系と、RNAとタンパク質の新しい解析技術を連携させ、病原性調節に働く新規RNA相互作用因子を網羅的に同定する。さらに、RNA相互作用因子が引き起こすRNAの質と量の調節機構を解明し、細菌の病原性発現における役割を解明する。

Outline of Final Research Achievements

Staphylococcus aureus and Streptococcus pneumoniae are pathogenic bacteria that cause various diseases. In order to establish new therapeutic strategies against drug-resistant bacteria, it is necessary to understand the mechanisms of pathogenesis of these bacteria. In this study, we analyzed the biochemical properties of a novel nucleotidase and demonstrated that this enzyme degrades oxidized nucleotides, leading to oxidative stress resistance in S. aureus, and functions in the development of pathogenicity. In the course of our research, we also discovered the reaction of aggregation formation by S. aureus in the plasma of silkworms. Analysis using gene-deficient strains suggested that the aggregation formation plays an important role in the development of pathogenicity of S. aureus.

Academic Significance and Societal Importance of the Research Achievements

本研究は，黄色ブドウ球菌の新規ヌクレオチド分解酵素を解析することにより，黄色ブドウ球菌が酸化ヌクレオチドを分解することにより酸化ストレス抵抗性を獲得することを発見した。細菌が多細胞生物への感染を可能とする新たな分子機構を明らかにした点で学術的意義がある。また，本酵素に対する阻害剤は新たな細菌感染症治療薬の創出につながる点で社会的意義がある。さらに，カイコプラズマ中における黄色ブドウ球菌の凝集塊形成の発見は，哺乳類と昆虫という異なる宿主間で保存された黄色ブドウ球菌の病原性発現ストラテジーの一端を明らかにした点で学術的意義がある。

Research Products

• [Journal Article] Proteolytic cleavage of HLA class II by human neutrophil elastase in pneumococcal pneumonia (2021)
  • Author(s): Hisanori Domon, Tomoki Maekawa, Toshihito Isono, Kazuyuki Furuta, Chikara Kaito, Yutaka Terao
  • Journal Title: Sci Rep Volume: 11 Issue: 1 Pages: 2432-2432
  • DOI: 10.1038/s41598-021-82212-5
  • Peer Reviewed / Open Access
• [Journal Article] Total Syntheses and Chemical Biology Studies of Hymeglusin and Fusarilactone A, Novel Circumventors of β-Lactam Drug Resistance in Methicillin-Resistant Staphylococcus aureus (2021)
  • Author(s): Kanaida M, Kimishima A, Eguchi S, Iwatsuki M, Watanabe Y, Honsho M, Hirose T, Noguchi Y, Nonaka K, Sennari G, Matsui H, Kaito C, Hanaki H, Asami Y, Sunazuka T.
  • Journal Title: ChemMedChem. Volume: in press. Issue: 13 Pages: 2106-2111
  • DOI: 10.1002/cmdc.202100219
  • Peer Reviewed
• [Journal Article] Animal infection models using non-mammals (2020)
  • Author(s): Chikara Kaito, Kanade Murakami, Lina Imai, Kazuyuki Furuta
  • Journal Title: Microbiology and immunology Volume: 64 Issue: 9 Pages: 585-592
  • DOI: 10.1111/1348-0421.12834
  • NAID: 120006953505
  • Peer Reviewed / Open Access
• [Journal Article] Epidemiological study on the relationship between toxin production and psm‐mec mutations in MRSA isolates in Thailand (2020)
  • Author(s): Tabuchi Fumiaki、Lulitanond Aroonlug、Lulitanond Viraphong、Thunyaharn Sudaluck、Kaito Chikara
  • Journal Title: Microbiology and Immunology Volume: 64 Issue: 3 Pages: 219-225
  • DOI: 10.1111/1348-0421.12764
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Tree of motility;A proposed history of motility systems in the tree of life (2020)
  • Author(s): M Miyata, R C Robinson, T QP Uyeda, Y Fukumori, S Fukushima, S Haruta, M Homma, K Inaba, M Ito, C Kaito, K Kato, TKenri, Y Kinosita, S Kojima, T Minamino, H Mori, S Nakamura, D Nakane, K Nakayama, M Nishiyama, S Shibata, K Shimabukuro, M Tamakoshi, A Taoka, Y Tashiro, ITulum, HiWada, K Wakabayashi
  • Journal Title: Genes to Cells Volume: 25 Issue: 1 Pages: 6-21
  • DOI: 10.1111/gtc.12737
  • NAID: 120006881482
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dataset for de novo transcriptome assembly of the African bullfrog Pyxicephalus adspersus (2020)
  • Author(s): Yoshida N, Kaito C.
  • Journal Title: Data Brief. Volume: 30 Pages: 105388-105388
  • DOI: 10.1016/j.dib.2020.105388
  • NAID: 120006866144
  • Peer Reviewed / Open Access
• [Journal Article] Staphylococcus aureus aggregation in the plasma fraction of silkworm hemolymph. (2019)
  • Author(s): Ryuno, H., Nigo, F., Naguro, I., Sekimizu, K., and Kaito, C.
  • Journal Title: PLoS One Volume: 14 Issue: 5 Pages: e0217517-e0217517
  • DOI: 10.1371/journal.pone.0217517
  • NAID: 120006780367
  • Peer Reviewed / Open Access
• [Journal Article] Identification of 2H phosphoesterase superfamily proteins with 2′-CPDase activity (2019)
  • Author(s): Mitsutomi Shuhei、Akimitsu Nobuyoshi、Sekimizu Kazuhisa、Kaito Chikara
  • Journal Title: Biochimie Volume: 165 Pages: 235-244
  • DOI: 10.1016/j.biochi.2019.08.008
  • Peer Reviewed
• [Presentation] 病原体進化の要因となる病原体宿主相互作用 (2021)
  • Author(s): 垣内力
  • Organizer: 第94回日本生化学会大会 シンポジウム（オンライン開催）
  • Invited
• [Presentation] MRSAの病原性制御機構 (2020)
  • Author(s): 垣内力
  • Organizer: 第94回日本感染症学会総会 シンポジウム
  • Invited