Whole-genome analysis for drug-resistance and pathogenicity of Aspergillus fumigatus

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07001
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: Chiba University
• Principal Investigator: Takahashi Hiroki 千葉大学, 真菌医学研究センター, 准教授 (60548460)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 病原真菌 / アスペルギルスフミガタス / 薬剤耐性 / ゲノム / 集団構造

Outline of Final Research Achievements

Aspergillus fumigatus is a pathogenic fungus with a global distribution. Although azole-resistant TR-mutants are widely distributed, a few TR-mutants have been isolated in Japan. The emergence of azole-resistant A. fumigatus (ARAf) other than the TR-mutants is a problem in Japan. In this study, we analyzed the genome sequences of 171 strains from Japan as well as the antifungal susceptibility of these strains. Next, we conducted a population analysis of 876 strains by combining the available genomic data for strains isolated worldwide, which were grouped in six clades. We observed the geographic characteristics of clades such as Clade 2 where the strains from Japan were over-represented. Finally, the genomic loci associated with azole resistance were detected on the basis of a genome-wide association study. Thus, we revealed the complexity of the genomic mechanism underlying the emergence of ARAf strains as well as the genomic diversity of A. fumigatus in Japan.

Free Research Field

ゲノム微生物学

Academic Significance and Societal Importance of the Research Achievements

アスペルギルスフミガタスの薬剤耐性化に寄与する遺伝子座を同定した。このことにより、感染菌の系統を評価することで、薬剤耐性化が起こり得るかの予測にも繋げることが可能となる。さらに診断に応用されれば、治療中に薬剤耐性化のリスク評価が可能となり、治療方針の先鋭化につながるなど、医療への応用が期待される。一方で、真菌はペニシリンに代表される創薬資源として重要であるため、本研究で産生されたゲノムデータの利活用により、新規有用物質の発見が期待される。