Infection control targeting Bacterial immunity taxi

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16230
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Infectious disease medicine
• Research Institution: Kyoto Pharmaceutical University (2019); Teikyo University (2017-2018)
• Principal Investigator: Kamoshida Go 京都薬科大学, 薬学部, 助教 (40707410)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: アシネトバクター / 好中球 / 細菌-宿主相互作用 / NETs / 細胞接着 / コリスチン / LPS / リゾチーム

Outline of Final Research Achievements

In the present study, we researched that focused on the mechanism by which Acinetobacter baumannii avoid from host immune defense and anti-microbial drugs. First, we investigated the effect of A. baumannii on the formation of neutrophil extracellular traps (NETs), a novel neutrophil defense mechanism against bacteria. As a result, it was revealed that A. baumannii inhibits NETs formation by suppressing neutrophil adhesion. Also, A. baumannii easily acquires drug resistance, and frequently shows resistance to colistin, which targets LPS (lipopolysaccharide). Next, we investigated the mechanisms of resistance to colistin, and the clearance mechanism of the colistin-resistant strain. A. baumannii was found to be resistant to colistin by LPS-deficient, but easily killed by lysozyme produced by neutrophils. In this study, it is expected that some of the competition between A. baumannii-host will be clarified, contributing to treatment and control of the bacteria infection.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

近年，好中球の新規感染防御機構である好中球細胞外トラップ (NETs) が注目を集めている．多くの病原性細菌が，NETs を誘導することが報告されているが，Acinetobacter baumannii は，病原性細菌であるにもかかわらず，NETs 形成を阻害することを明らかにした．本研究は，病原性細菌が NETs 形成を阻害することを示した最初の報告である．
A. baumannii は，多剤耐性グラム陰性菌による重篤感染症に最後の砦として使用されるコリスチンに対し，標的である LPS を欠損することで耐性を示す．しかし，LPS 欠損株は，宿主防御により排除されやすいことを明らかとした．