頑固な細菌感染症を治療する「トロイの木馬」の可能性が発見される(Possible ‘Trojan Horse’ found for treating stubborn bacterial infections)

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2024-03-05 ワシントン州立大学(WSU)

ワシントン州立大学の研究者らによる新しい研究では、細菌は死の信号を送るように騙され、致命的な感染を引き起こす保護的な粘着物の成長を停止することが示されました。この発見は、将来的には難治性の感染症を治療するための抗生物質の代替手段として利用される可能性があります。研究は、バイオフィルムという固い家に隠れる細菌の一部を殺すために、死の細胞外小胞(D-EVs)と名付けられたメッセンジャーを使用し、実験室での細菌コミュニティの成長を最大99.99%まで減少させることが示されました。

<関連情報>

緑膿菌バイオフィルム由来の条件付き細胞外小胞の二重の役割: 細菌のバイオフィルム増殖を促進・抑制する Dual roles of the conditional extracellular vesicles derived from Pseudomonas aeruginosa biofilms: Promoting and inhibiting bacterial biofilm growth

Marwa Gamal Saad, Haluk Beyenal, Wen-Ji Dong
Biofilm  Available online:6 February 2024
DOI:https://doi.org/10.1016/j.bioflm.2024.100183

頑固な細菌感染症を治療する「トロイの木馬」の可能性が発見される(Possible ‘Trojan Horse’ found for treating stubborn bacterial infections)

Highlights

•Regulatory roles of bacterial extracellular vesicles in biofilm growth are culture condition dependent.

•D-EVs can prevent biofilm formation and treat pre-existing biofilms.

•Ferric ions enhance the power of the D-EVs in treating resilient aged biofilms.

•Ferroptosis may be involved in the action of the D-EVs against biofilms.

Abstract

Antibiotic-resistant biofilm infections have emerged as public health concerns because of their enhanced tolerance to high-dose antibiotic treatments. The biofilm life cycle involves multiple developmental stages, which are tightly regulated by active cell-cell communication via specific extracellular signal messengers such as extracellular vesicles. This study was aimed at exploring the roles of extracellular vesicles secreted by Pseudomonas aeruginosa at different developmental stages in controlling biofilm growth. Our results show that extracellular vesicles secreted by P. aeruginosa biofilms during their exponential growth phase (G-EVs) enhance biofilm growth. In contrast, extracellular vesicles secreted by P. aeruginosa biofilms during their death/survival phase (D-EVs) can effectively inhibit/eliminate P. aeruginosa PAO1 biofilms up to 4.8-log10 CFU/cm2. The inhibition effectiveness of D-EVs against P. aeruginosa biofilms grown for 96 h improved further in the presence of 10–50 μM Fe3+ ions. Proteomic analysis suggests the inhibition involves an iron-dependent ferroptosis mechanism. This study is the first to report the functional role of bacterial extracellular vesicles in bacterial growth, which depends on the developmental stage of the parent bacteria. The finding of D-EV-activated ferroptosis-based bacterial death may have significant implications for preventing antibiotic resistance in biofilms.

有機化学・薬学
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