Study on the escape mechanism of multidrug-resistant bacteria from host defense mechanism and development of new therapeutic method

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10032
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Teikyo University
• Principal Investigator: ONO Yasuo 帝京大学, 医学部, 教授 (10177272)
• Co-Investigator(Kenkyū-buntansha): 西田 智 帝京大学, 医学部, 講師 (10409386) ; 永川 茂 帝京大学, 医学部, 講師 (50266300) ; 佐藤 義則 帝京大学, 医学部, 助教 (90455402)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 多剤耐性菌 / アシネトバクタアー / 好中球 / マクロファージ / 生体防御機構 / バイオフィルム / 抗菌薬 / 昆虫モデル

Outline of Final Research Achievements

Acinetobacter baumannii (A.b) suppresses NETs formation in neutrophils. MDRA clinical isolates have high catalase-producing ability and survive and proliferate in the phagosome even after being phagocytosed by macrophages. Co-culture of A.b and its lipopolysaccharide (LPS) with mast cells and adipocytes enhanced the production of inflammatory cytokines and chemokines.　The sub-MICs　of tigecycline suppressed the biofilm formation of MDRA, while colistin (CL) enhanced it. The virulence of the LPS-deficient A.b strain was reduced. We analyzed the resistance genes of multidrug-resistant strains such as KPC-producing Klebsiella pneumoniae isolated in our hospital.　Pathological findings in A.b mouse pneumonia model were compared with Pseudomonas aeruginosa.
We established a drug efficacy evaluation system for antibacterial drugs using the MDRA insect infection model.

Free Research Field

感染症学、感染免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究によりMDRAの病原性低下を狙った新規治療法の開発や免疫不全患者の感染症治療における新たな免疫補助療法に関する基礎的知見が得られたと思われる。MDRA昆虫感染モデルを用いた抗菌薬の薬効評価系の確立は、多剤耐性菌に対する新規抗菌薬の有効性をみるためのスクリーニングなどに有用と思われる。