Biofilm promoting factors for aspergillus in human serum and azole resistance of the fungus

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07103
• 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: KAMEI KATSUHIKO 千葉大学, 真菌医学研究センター, 教授 (10214545)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: aspergillus / biofilm / azole resistance / fungus ball / serum component

Outline of Final Research Achievements

We searched for biofilm formation-promoting factors of Aspergillus fumigatus in human serum. First, a simple biofilm formation assay was newly established. Then using this method, we analyzed human serum to find biofilm formation promoting factors. We found potent activity in the fraction below 10 kDa, and this activity was as intense as that of fetuin A. We also found that high-density lipoprotein (HDL) complexes in serum strongly inhibited the growth of A. fumigatus.
In the search for biofilm-forming gene profile in A. fumigatus, we collected fungi obtained from the same patients over time and examined their drug susceptibility, biofilm-forming ability, and genetic mutations. As a result, we identified gene mutations with the potentials to significantly suppress biofilm production.

Free Research Field

医真菌学

Academic Significance and Societal Importance of the Research Achievements

本研究により、アスペルギルスが感染時に、複数のヒト血清成分を自らのbiofilm形成に利用していることが明らかになったが、同時に、全く予想していなかった一部の血清成分はアスペルギルスに対して抑制的に作用していることも見いだされた．また、比較ゲノム法により、biofilm形成促進に関与する遺伝子候補が確認された。
今後、これらの血清中の有効成分の解析やbiofilm形成遺伝子の解析により、難治化及び耐性化の原因であるbiofilm形成の抑制を標的とした全く新しい治療戦略への道が示された．