Establishment of the molecular bases for development of the next-generation Streptococcus pneumoniae vaccine

• Project/Area Number: 25460555
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including mycology)
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: OGAWA Michinaga 国立感染症研究所, その他部局等, 室長 (80361624)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 肺炎球菌 / 病原性 / 次世代ワクチン / 細胞内膜輸送 / 細胞内生存 / エフェクター / 細胞内生存性 / 病原因子

Outline of Final Research Achievements

In this study, I aimed at revealing the function of the pneumococcal virulence factor and the interaction of intracellular pneumococci and host cells.
As a result of intracellular survivability test using 40 kinds of gene-targeted deletion mutants, it was revealed that 14 pneumococcal virulence factors play pivotal role in the survivability of pneumococci in host cells.
Next, I examined 58 kinds of Rab proteins in their co-localization with intracellular pneumococci, and 10 Rab protein were revealed to be targeted to the endosomes engulfing pneumococci.

Research Products

• [Journal Article] Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). (2016)
  • Author(s): Klionsky DJ et al.
  • Journal Title: Autophagy Volume: 12 Pages: 1-222
  • Peer Reviewed
• [Journal Article] Evaluation of streptococcal toxic shock-like syndrome caused by group B streptococcus in adults in Japan between 2009 and 2013. (2015)
  • Author(s): 2.Ikebe T, Chiba K, Shima T, Masuda C, Okuno R, Ohya H, Ogata K, Katsukawa C, Kawahara R, Tominaga K, Yabata J, Tada Y, Okabe N, Watanabe H, Chang B, Ogawa M, Ohnishi M, the Working group for beta-hemolytic streptococci in Japan.
  • Journal Title: J Infection Chemotherpy Volume: 21 Issue: 3 Pages: 207-211
  • DOI: 10.1016/j.jiac.2014.12.002
  • Peer Reviewed
• [Journal Article] Macroautophagy is essential for killing of intracellular Burkholderia pseudomallei in human neutrophils. (2015)
  • Author(s): Rinchai D, Riyapa D, Buddhisa S, Utispan K, Titball RW, Stevens MP, Stevens JM, Ogawa M, Tanida I, Koike M, Uchiyama Y, Ato M, Lertmemongkolchai G.
  • Journal Title: Autophagy Volume: 11 Issue: 5 Pages: 748-755
  • DOI: 10.1080/15548627.2015.1040969
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Increased prevalence of group A streptococcus isolates in streptococcal toxic shock syndrome cases in Japan from 2010–2012. (2015)
  • Author(s): 1.Ikebe T, Tominaga K, Shima T, Okuno R, Kubota H, Ogata K, Chiba K, Katsukawa C, Ohya H, Tada Y, Okabe N, Watanabe H, Ogawa M, Ohnishi M, Working Group for Beta-hemolytic Streptococci in Japan.
  • Journal Title: Epidemiology Infection Volume: 143 Issue: 4 Pages: 864-872
  • DOI: 10.1017/s0950268814001265
  • Peer Reviewed
• [Journal Article] Shigella IpaH7.8 E3 ligase targets glomulin and activates inflammasomes to demolish macrophages (2014)
  • Author(s): Suzuki S et.al
  • Journal Title: Proc Natl Acad Sci USA Volume: 111 Issue: 40
  • DOI: 10.1073/pnas.1324021111
  • Peer Reviewed
• [Journal Article] Epigenetic silencing of miR-210 increases the proliferation of gastric epithelium during chronic Helicobacter pylori infection (2014)
  • Author(s): Kiga K et.al
  • Journal Title: Nat Commun Volume: 5 Issue: 1 Pages: 4497-4497
  • DOI: 10.1038/ncomms5497
  • Peer Reviewed / Open Access
• [Journal Article] Increased prevalence of group A streptococcus isolates in streptococcal toxic shock syndrome cases in Japan from 2010–2012 (2014)
  • Author(s): Ikebe, T., Tominaga, K., Shima, T., Okuno, R., Kubota, H., Ogata, K., Chiba, K., Katsukawa, C., Ohya, H., Tada, Y., Okabe, N., Watanabe, H., Ogawa, M., Ohnishi, M., and the Working Group For Beta-Hemolytic streptococci In Japan.
  • Journal Title: Epidemiology and Infection Volume: 未定
  • Peer Reviewed
• [Journal Article] Phospholipase C-related catalytically inactive protein participates in the autophagic elimination of Staphylococcus aureus infecting mouse embryonic fibroblasts. (2014)
  • Author(s): Harada-Hada, K., Harada, K., Kato, F., Hisatsune, J., Tanida, I., Ogawa, M., Asano, S., Sugai, M., Hirata M., & Kanematsu. T.
  • Journal Title: PLoS One Volume: 未定
  • Peer Reviewed
• [Journal Article] Autophagy controls an intrinsic host defense to bacteria by promoting epithelial cell survival : a murine model. (2013)
  • Author(s): Chang SY, Lee SN, Yang JY, Kim DW, Yoon JH, Ko HJ, Ogawa M, Sasakawa C, Kweon MN.
  • Journal Title: PLoS One. Volume: 8 Issue: 11 Pages: e81095-e81095
  • DOI: 10.1371/journal.pone.0081095
  • Peer Reviewed
• [Journal Article] The Shigella OspC3 effector inhibits Cspase-4, antagonizes inflammatory cell death, and promotes epithelial infection (2013)
  • Author(s): Kobayashi T, et. al
  • Journal Title: Cell Host Microbe Volume: 13 Issue: 5 Pages: 570-583
  • DOI: 10.1016/j.chom.2013.04.012
  • Peer Reviewed
• [Presentation] 病原細菌に対するオートファジー認識機構とその阻害機構 (2015)
  • Author(s): 小川道永
  • Organizer: 第88回日本細菌学会総会
  • Place of Presentation: 長良川国際会議場
  • Year and Date: 2015-03-26
• [Presentation] 細胞内侵入細菌と選択的オートファジーの攻防
  • Author(s): 小川道永
  • Organizer: 第24回日本生体防御学会学術総会
  • Place of Presentation: 熊本
  • Invited