Biophysical basis of phage liquid crystalline droplet-mediated antibiotic tolerance in pathogenic bacteria

Biophysical basis of phage liquid crystalline droplet-mediated antibiotic tolerance in pathogenic bacteria
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噬菌体液晶液滴介导的病原菌抗生素耐受的生物物理基础

DOI:
10.1101/2022.12.13.520211
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发表时间:
2022
期刊:
--
影响因子:
--
通讯作者:
Böhning J
Böhning J
中科院分区:
--
文献类型:
--
作者:
Böhning J

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Inoviruses是一种丰富的丝状真菌,感染许多原核生物门,在那里它们可以共生地促进宿主适应性并增加细菌的毒力。由于其独特的性质,丝形病毒也被用于生物技术中的噬菌体展示和作为模型用于研究胶体棒的相行为。由细菌分泌的Inoviral RNA可以自组装成液晶液滴,其保护生物膜中的细菌细胞免受抗生素的侵害,然而,控制这种液滴形成的因素和抗生素保护机制知之甚少。在这里,我们调查的结构,生物物理,和保护性的液晶液滴形成的铜绿假单胞菌和大肠杆菌inoviral。我们报告了一个冷冻电镜结构的衣壳高度研究E。colifd噬菌体的生化特性与来自P.铜绿。我们发现,FD和Pf4形成液晶液滴与不同的形态所管辖的基础噬菌体颗粒的几何形状和生物物理学,而不是他们的表面生化特性。最后,我们表明,这些形态上不同的液滴由任一噬菌体可以保护杆状细菌从抗生素治疗,尽管与细胞的关联模式不同。这项研究推进了我们对噬菌体组装成液晶液滴的理解,并提供了丝状分子如何在拥挤条件下保护细菌免受外来分子的影响的见解,这些分子存在于生物膜或感染的宿主组织中。
Inoviruses are abundant filamentous phages infecting numerous prokaryotic phyla, where they can symbiotically promote host fitness and increase bacterial virulence. Due to their unique properties, inoviruses have also been utilised in biotechnology for phage display and as models for studying phase behaviour of colloidal rods. Inoviral phages secreted by bacteria can self-assemble into liquid crystalline droplets that protect bacterial cells in biofilms from antibiotics, however, factors governing the formation of such droplets and the mechanism of antibiotic protection are poorly understood. Here, we investigate the structural, biophysical, and protective properties of liquid crystalline droplets formed byPseudomonas aeruginosaandEscherichia coliinoviral phages. We report a cryo-EM structure of the capsid from the highly studiedE. colifd phage, revealing distinct biochemical properties of fd compared to Pf4 phage fromP. aeruginosa. We show that fd and Pf4 form liquid crystalline droplets with diverse morphologies governed by the underlying phage particle geometry and biophysics, rather than their surface biochemical properties. Finally, we show that these morphologically diverse droplets made of either phage can protect rod-shaped bacteria from antibiotic treatment, despite differing modes of association with cells. This study advances our understanding of phage assembly into liquid crystalline droplets, and provides insights into how filamentous molecules protect bacteria from extraneous molecules under crowding conditions, which are found in biofilms or on infected host tissues.
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