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Extracellular matrix stiffness modulates host-bacteria interactions and antibiotic therapy of bacterial internalization
Biomaterials ( IF 12.8 ) Pub Date : 2021-08-27 , DOI: 10.1016/j.biomaterials.2021.121098
Xiaoye Liu 1 , Kui Zhu 2 , Xiaocen Duan 3 , Pudi Wang 3 , Yiming Han 3 , Wenjing Peng 2 , Jianyong Huang 3
Affiliation  

Pathogenic bacteria evolve multiple strategies to hijack host cells for intracellular survival and persistent infections. Previous studies have revealed the intricate interactions between bacteria and host cells at genetic, biochemical and even single molecular levels. Mechanical interactions and mechanotransduction exert a crucial impact on the behaviors and functions of pathogenic bacteria and host cells, owing to the ubiquitous mechanical microenvironments like extracellular matrix (ECM) stiffness. Nevertheless, it remains unclear whether and how ECM stiffness modulates bacterial infections and the sequential outcome of antibacterial therapy. Here we show that bacteria tend to adhere to and invade epithelial cells located on the regions with relatively high traction forces. ECM stiffness regulates spatial distributions of bacteria during the invasion through arrangements of F-actin cytoskeletons in host cells. Depolymerization of cytoskeletons in the host cells induced by bacterial infection decreases intracellular accumulation of antibiotics, thus preventing the eradication of invaded bacterial pathogens. These findings not only reveal the key regulatory role of ECM stiffness, but suggest that the coordination of cytoskeletons may provide alternative approaches to improve antibiotic therapy against multidrug resistant bacteria in clinic.



中文翻译:

细胞外基质硬度调节宿主-细菌相互作用和细菌内化的抗生素治疗

病原菌进化出多种策略来劫持宿主细胞以实现细胞内存活和持续感染。先前的研究揭示了细菌和宿主细胞在遗传、生化甚至单分子水平上的复杂相互作用。机械相互作用和机械转导由于细胞外基质 (ECM) 刚度等无处不在的机械微环境,对致病细菌和宿主细胞的行为和功能产生至关重要的影响。然而,目前尚不清楚 ECM 僵硬是否以及如何调节细菌感染和抗菌治疗的连续结果。在这里,我们表明细菌倾向于粘附并侵入位于具有相对较高牵引力区域的上皮细胞。ECM 刚度通过宿主细胞中 F-肌动蛋白细胞骨架的排列调节入侵过程中细菌的空间分布解聚由细菌感染引起的宿主细胞中细胞骨架的减少减少了细胞内抗生素的积累,从而阻止了入侵的细菌病原体的根除。这些发现不仅揭示了 ECM 刚度的关键调节作用,而且表明细胞骨架的协调可能提供替代方法来改善临床上针对多药耐药细菌的抗生素治疗。

更新日期:2021-09-01
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