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A photo-sensitizable phage for multidrug-resistant Acinetobacter baumannii therapy and biofilm ablation
Chemical Science ( IF 7.6 ) Pub Date : 2020-11-16 , DOI: 10.1039/d0sc04889e
Bei Ran 1 , Yuyu Yuan 2 , Wenxi Xia 1 , Mingle Li 1 , Qichao Yao 1 , Zuokai Wang 1 , Lili Wang 2 , Xiaoyu Li 2 , Yongping Xu 2 , Xiaojun Peng 1
Affiliation  

Antibiotic abuse causes the emergence of bacterial resistance. Photodynamic antibacterial chemotherapy (PACT) has great potential to solve serious bacterial resistance, but it suffers from the inefficient generation of ROS and the lack of bacterial targeting ability. Herein, a unique cationic photosensitizer (NB) and bacteriophage (ABP)-based photodynamic antimicrobial agent (APNB) is developed for precise bacterial eradication and efficient biofilm ablation. Thanks to the structural modification of the NB photosensitizer with a sulfur atom, it displays excellent reactive oxygen species (ROS)-production ability. Moreover, specific binding to pathogenic microorganisms can be provided by bacteriophages. The developed APNB has multiple functions, including bacteria targeting, near-infrared fluorescence imaging and combination therapy (PACT and phage therapy). Both in vitro and in vivo experiments prove that APNB can efficiently treat A. baumannii infection. Particularly, the recovery from A. baumannii infection after APNB treatment is faster than that with ampicillin and polymyxin B in vivo. Furthermore, the strategy of combining bacteriophages and photosensitizers is employed to eradicate bacterial biofilms for the first time, and it shows the excellent biofilm ablation effect as expected. Thus, APNB has huge potential in fighting against multidrug-resistant bacteria and biofilm ablation in practice.

中文翻译:

用于耐多药鲍曼不动杆菌治疗和生物膜消融的光敏噬菌体

抗生素滥用会导致细菌耐药性的出现。光动力抗菌化疗(PACT)具有解决严重细菌耐药性的巨大潜力,但存在活性氧生成效率低、细菌靶向能力不足等问题。在此,开发了一种独特的基于阳离子光敏剂 (NB) 和噬菌体 (ABP) 的光动力抗菌剂 (APNB),用于精确的细菌根除和有效的生物膜消融。由于 NB 光敏剂用硫原子进行了结构修饰,它表现出优异的活性氧 (ROS) 生成能力。此外,噬菌体可以提供与病原微生物的特异性结合。开发的APNB具有多种功能,包括细菌靶向,近红外荧光成像和联合治疗(PACT 和噬菌体治疗)。两个都体外体内实验证明APNB可以有效治疗鲍曼不动杆菌感染。特别是,APNB 治疗后鲍曼不动杆菌感染的恢复快于体内氨苄青霉素和多粘菌素B。此外,首次采用噬菌体和光敏剂相结合的策略根除细菌生物膜,并显示出预期的优异生物膜消融效果。因此,APNB 在实际对抗多重耐药菌和生物膜消融方面具有巨大潜力。
更新日期:2020-11-25
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