Mechanism of a streptococcal toxic shock syndrome to non-streptococcal toxic shock syndrome transition in the novel-type Streptococcus pyogenes isolates

2019 Fiscal Year Final Research Report

• Project/Area Number: 15K09575
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Nagoya City University
• Principal Investigator: Tatsuno Ichiro 名古屋市立大学, 医薬学総合研究院(医学), 講師 (50311642)
• Co-Investigator(Kenkyū-buntansha): 長谷川 忠男 名古屋市立大学, 医薬学総合研究院(医学), 教授 (10314014) ; 井坂 雅徳 名古屋市立大学, 医薬学総合研究院(医学), 助教 (40336673)
• Project Period (FY): 2015-04-01 – 2020-03-31
• Keywords: A群レンサ球菌 / 病原性 / ゲノム / fabT

Outline of Final Research Achievements

Streptococcus pyogenes is a causative agent of streptococcal toxic shock syndrome (STSS). Recently, we showed that the regions encoding the SalR-SalK, a two-component regulatory system, were deleted in some emm 1-type isolates (named as “novel-type”). In this study, the two novel “STSS” isolates 10-85 and 11-171 were more virulent than the two novel “non-STSS” isolates 11O-2 and 11T-3 when examined using a mouse model of invasive infection. Genome sequencing experiments using the three strains 10-85, 11-171, and 11O-2 detected only one single nucleotide polymorphism that causes a non-synonymous mutation in fabT encoding a transcriptional regulator in strain 11O-2. Loss of fabT reduced the high level of virulence observed in the STSS isolates to that in the non-STSS isolates, and introduction of an intact fabT compensated the lower virulence of 11O-2, suggesting that the mutation in fabT is involved in the differential virulence among the novel-type clinical isolates.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

A群レンサ球菌新型株（特徴として、SalR-SalK遺伝子を含む領域を欠損している）には病原性の高い株と病原性の低い株の２種類が存在する。この病原性の違いが、fabT遺伝子の変異に依存していることを突き止めた。fabT遺伝子に変異を持つ株が一定の割合で出現することは、海外のグループからも報告された。しかし、病原性が低下するようなfabT遺伝子の変異が自然界で起こる理由についてはいまだ不明である。