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金纳米颗粒通过抑制生物膜的形成以及破坏霍乱毒素的产生和结构,从而降低霍乱弧菌的致病性。

The gold nanoparticle reduces Vibrio cholerae pathogenesis by inhibition of biofilm formation and disruption of the production and structure of cholera toxin.

机构信息

Department of Biochemistry, Bose Institute, P1/12 CIT Scheme VIIM, Kolkata, 700054, India.

Division of Molecular Pathophysiology, National Institute of Cholera & Enteric Diseases, P-33 CIT Road, Scheme XM, Beliaghata, Kolkata, 700010, India.

出版信息

Colloids Surf B Biointerfaces. 2021 Aug;204:111811. doi: 10.1016/j.colsurfb.2021.111811. Epub 2021 Apr 30.

DOI:10.1016/j.colsurfb.2021.111811
PMID:33965751
Abstract

Formation of biofilm by Vibrio cholerae plays a crucial role in pathogenesis and transmission of cholera. Lower infective dose of the biofilm form of V. cholerae compared to the planktonic counterpart, and its antibiotic resistance, make it challenging to combat cholera. Nanoparticles may serve as an effective alternative to conventional antibiotics for targeting biofilms and virulence factors. We explored the effectiveness of gold nanoparticles (AuNPs) of different size and shape (spherical: AuNS10 and AuNS100, and rod: AuNR10, the number indicating the diameter in nm) on both the inhibition of formation and eradication of biofilm of the two biotypes of V. cholerae, classical (VcO395) and El Tor (VcN16961). Inhibition of biofilm formation by spherical AuNPs was observed for both the biotypes. Considering eradication, the biofilms for both, particularly El Tor, was destroyed using both the AuNSs, AuNS100 showing higher efficacy. AuNR10 did not affect the biofilm of either biotype. Micrographs of small intestinal sections of VcO395-infected mice indicated the inhibition of biofilm formation by both AuNSs. We also studied the effect of these AuNPs on the structure of cholera toxin (CT), the major toxin produced by V. cholerae. Far-UV CD showed both AuNR10 and AuNS100 compromised the structure of CT, which was also validated from the reduction of fluid accumulation in mice ileal loop. Western blot analysis revealed the reduction of CT production upon treatment with AuNPs. AuNS100 seems to be the best suited to inhibit the formation or destruction of biofilm, as well as to disrupt CT production and function.

摘要

霍乱弧菌生物膜的形成在霍乱的发病机制和传播中起着至关重要的作用。与浮游生物相比,生物膜形式的霍乱弧菌的感染剂量更低,而且具有抗生素耐药性,这使得对抗霍乱变得具有挑战性。纳米颗粒可以作为传统抗生素的有效替代品,用于靶向生物膜和毒力因子。我们探索了不同大小和形状的金纳米颗粒(AuNPs)(球形:AuNS10 和 AuNS100,棒形:AuNR10,数字表示直径为纳米)对两种生物型霍乱弧菌(古典型(VcO395)和 El Tor 型(VcN16961))生物膜形成和消除的有效性。两种生物型的球形 AuNPs 均观察到抑制生物膜形成。考虑到消除作用,两种生物膜,特别是 El Tor 型,均被 AuNSs 破坏,其中 AuNS100 表现出更高的功效。AuNR10 对两种生物型的生物膜均无影响。感染 VcO395 的小鼠小肠切片的显微镜照片表明,两种 AuNS 均可抑制生物膜形成。我们还研究了这些 AuNPs 对霍乱毒素(CT)结构的影响,CT 是霍乱弧菌产生的主要毒素。远紫外 CD 显示,AuNR10 和 AuNS100 均破坏了 CT 的结构,这也从小鼠回肠环中液体积累减少得到了验证。Western blot 分析显示,AuNPs 处理后 CT 的产生减少。AuNS100 似乎最适合抑制生物膜的形成或破坏,以及破坏 CT 的产生和功能。

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