Study on the escape mechanism of multidrug-resistant bacteria from host defense mechanism and development of new therapeutic method
| 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
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| 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 / アシネトバクター・バウマニ / リポ多糖体 / 好中球細胞外トラップ / 昆虫感染モデル / KPC産生肺炎桿菌 / マウス肺感染モデル / MDRA / マスト細胞 / 脂肪細胞 / リポ多糖体（LPS) / 感染モデル / 感染症 / 薬剤耐性細菌 / 病原因子 / 抗体療法 |
|---|
| 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.
|
| 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。
|
Report
(4 results)
Research Products
(36 results)
-
[Journal Article] Lipopolysaccharide-deficient Acinetobacter baumannii due to colistin resistance is killed by neutrophil-produced lysozyme2020
Author(s)
Kamoshida G, Akaji T, Takemoto N, Suzuki Y, Sato Y, Kai D, Hibino T, Yamaguchi D, Kikuchi-Ueda T, Nishida S, Unno Y, Tansho-Nagakawa S, Ubagai T, Miyoshi-Akiyama T, Oda M, Ono Y
-
Journal Title
Front Microbiol
Volume: 11
Pages: 573-573
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Emergence of Colistin-Resistant and KPC-producing Klebsiella pneumoniae in ST11 international High-Risk Clone.2017
Author(s)
Satoshi Nishida, Takane Kikuchi Ueda, Tsuneyuki Ubagai, Yuka Unno, Go Kamoshida, Yoshinori Sato, Shigeru Tnasho Nagakawa, Miwa Asahara, Shinobu Ishidagki, Taiji Furukawa, Yasuo Ono
Organizer
ASM Microbe 2017 in New Orleans
Related Report
Int'l Joint Research
