Comprehensive transcriptome analysis of group A streptococci using the murine invasive model reveals a key gene network causing severe invasive diseases

2018 Fiscal Year Final Research Report

• Project/Area Number: 15H05654
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Bacteriology (including mycology)
• Research Institution: Jichi Medical University
• Principal Investigator: Watanabe Shinya 自治医科大学, 医学部, 准教授 (60614956)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: レンサ球菌 / 劇症型レンサ球菌感染症 / マウス感染モデル / ゲノム解析 / 遺伝子発現

Outline of Final Research Achievements

Group A streptococci (GAS) can acquire a hypervirulent phenotype in transitioning from localized to systemic infections. This involves mutations in global regulator genes, such as csrS, followed by broad transcriptional alterations. However, the key genes controlled by the regulators have not yet been fully determined. In this study, the entire genomes of randomly-selected animal-passed GAS colonies were sequenced, as was a sdaD2 strain. The significantly reduced csrS mutation frequency in sdaD2 was accompanied by increases in mutations of other regulatory genes, such as rocA. The in vivo transcriptome profiles of six mutated hypervirulent-associated regulators was evaluated by RNA sequencing to identify a set of genes responsible for the hypervirulent phenotype. Transcriptome analysis identified a network co-regulated by the regulators involved in transitioning to systemic disease. This gene cluster may be important in inducing severe systemic GAS infections.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

A群レンサ球菌はヒトに咽頭に常在する細菌である。A群レンサ球菌は、冬季の咽頭炎の原因菌であるにも関わらず、劇症型溶血性レンサ球菌感染症（STSS）のような致死率の高い感染症も同時に起こす。STSSの患者から分離された株は、転写調節因子に変異があり病原因子が高発現していることがわかっている。本研究では、マウス感染モデルを用いて、転写調節因子に変異がある高病原株が感染時に発現上昇する遺伝子の一群を同定した。