Identification and analysis of mutation genes found specifically in streptococcal toxic shock syndrome isolates

• Project/Area Number: 25460554
• 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: Ikebe Tadayoshi 国立感染症研究所, 細菌第一部, 主任研究官 (20333362)
• Co-Investigator(Renkei-kenkyūsha): ATO Manabu 国立感染症研究所, 免疫部, 部長 (20392318)
• 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: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 劇症型溶血性レンサ球菌感染症 / レンサ球菌 / 細菌 / 遺伝子 / A群レンサ球菌 / 遺伝子変異

Outline of Final Research Achievements

Streptococcus pyogenes (group A Streptococcus; GAS) is a widespread human pathogen and causes streptococcal toxic shock syndrome (STSS). STSS isolates have been previously shown to have high frequency mutations in the csrS/csrR (covS/covR) and/or rgg (ropB) genes, which are negative regulators of virulence. However, these mutations were found at low frequencies in emm1-genotyped isolates, the most prevalent STSS genotype. We sought to detect causal mutations of enhanced virulence in emm1 isolates lacking mutation(s) in the csrS/csrR and rgg genes. Two mutations associated with elevated virulence were found in the sic (a virulence gene) promoter and the csrR promoter. In vivo contribution of the sic promoter to pathogenicity and lethality was confirmed in a GAS mouse model. Frequency of the sic promoter mutation was significantly higher in STSS emm1 isolates than in non-invasive STSS isolates. Thus, this mutation plays a key role in the dynamics of virulence and STSS pathogenesis.

Research Products

• [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] 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] Updated model of group A Streptococcus M proteins based on a comprehensive worldwide study. (2013)
  • Author(s): McMillan DJ, Dreze P, Vu T, Bessen DE, Guglielmini J, Steer AC, Carapetis JR, Melderen LV, Sriprakash KS, Smeesters PR, The M Protein Study Group.
  • Journal Title: Clin Microbiol Infect Volume: 19 Issue: 5 Pages: E222-E229
  • DOI: 10.1111/1469-0691.12134
  • Peer Reviewed
• [Presentation] 劇症型溶血性レンサ球菌感染症 (2016)
  • Author(s): 池辺忠義
  • Organizer: 第89回日本細菌学会総会
  • Place of Presentation: 大阪国際交流センター
  • Year and Date: 2016-03-23
• [Presentation] Increase of group A streptococcus isolates in streptococcal toxic shock syndrome cases in Japan (2014)
  • Author(s): 池辺忠義、奥野ルミ、緒方喜久代、大屋日登美、渡邉治雄、小川道永、大西真
  • Organizer: 第87回日本細菌学会総会
  • Place of Presentation: 東京都
• [Presentation] The defensive role of immature myeloid cells in severe invasive group A Streptococcus infections (2014)
  • Author(s): 松村隆之、池辺忠義、阿戸学
  • Organizer: 第87回日本細菌学会総会
  • Place of Presentation: 東京都
• [Presentation] Fat-1 transgenic mice are more susceptive to severe invasive group A Streptococcus infections (2014)
  • Author(s): 土屋勅、松村隆之、池辺忠義、小林和夫、阿戸学
  • Organizer: 第87回日本細菌学会総会
  • Place of Presentation: 東京都