2023 Fiscal Year Final Research Report

Elucidation of the mechanisms of antibiotic tolerance in biofilm cells, focusing on the two-component regulatory systems

Research Project

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Project/Area Number	18K09535
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 57020:Oral pathobiological science-related
Research Institution	Kawasaki University of Medical Welfare (2021-2023) The University of Tokushima (2018-2020)
Principal Investigator	Murakami Keiji 川崎医療福祉大学, 医療技術学部, 教授 (10335804)
Co-Investigator(Kenkyū-buntansha)	天羽崇徳島大学, 大学院医歯薬学研究部(歯学域), 特任助教 (00803545) 藤猪英樹慶應義塾大学, 医学部(日吉), 教授 (50356250)
Project Period (FY)	2018-04-01 – 2024-03-31
Keywords	バイオフィルム / 抗菌薬抵抗性 / 2成分制御系 / 緑膿菌
Outline of Final Research Achievements	Biofilms formed in the body cause various chronic infections. Antibiotic tolerance has attracted attention as a reason why antibiotics are ineffective. We have reported that two-component regulatory systems also play important roles. To clarify the mechanism of antibiotic tolerance, we focused on the two-component regulatory systems, such as cbrA-B and phoB-R. Compared to the PAO1, the cbrB and phoB-deficient mutant showed low antibiotic tolerance in biofilm cells. We attempted to find genes directly controlled by the cbrA-B and phoB-R systems by CHIP-seq analysis, but could not achieve these results in this time. It was also revealed that antibiotic tolerance increased by environmental stress. These results indicate that P. aeruginosa acquires antibiotic tolerance due to environmental stresses such as biofilm formation, and that the two-component regulatory systems play an important role in this process.
Free Research Field	細菌学
Academic Significance and Societal Importance of the Research Achievements	緑膿菌バイオフィルムによる感染症は、慢性呼吸器感染症をはじめとして、医療の現場では問題となることが多い。現在の治療薬では十分な効果が得られないものの、新たな治療薬の開発の停滞は、世界的にも大きな問題となっており、感染症を取り巻く現状は非常に厳しい。我々の研究はまだ基礎的な段階であるものの、新たな治療薬の創出に向け、これまでにない薬剤のターゲットが存在することを示唆しており、新規治療薬の開発に大きく貢献することができるものと考えている。