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亚致死浓度的胶态纳米银制剂(Silversol®)可触发多重耐药铜绿假单胞菌中铁稳态和氮代谢的失调。

Sub-lethal concentration of a colloidal nanosilver formulation (Silversol®) triggers dysregulation of iron homeostasis and nitrogen metabolism in multidrug resistant Pseudomonas aeruginosa.

机构信息

Institute of Science, Nirma University, Ahmedabad, 382481, India.

Viridis BioPharma Pvt Ltd, Mumbai, India.

出版信息

BMC Microbiol. 2023 Oct 23;23(1):303. doi: 10.1186/s12866-023-03062-x.

Abstract

BACKGROUND

Pseudomonas aeruginosa is a notorious pathogen. Its multidrug resistant strains are listed among priority pathogens against whom discovery of novel antibacterial agents and, elucidation of new anti-pathogenicity mechanisms are urgently warranted. This study describes multiple antibacterial effects of a colloidal nano-silver formulation- Silversol® against a multi-drug resistant strain of P. aeruginosa.

RESULTS

Minimum inhibitory concentration (MIC) of Silversol® against P. aeruginosa was found to be 1.5 ppm; and at sub-MIC of 1 ppm, it was able to alter quorum-sensing regulated pigmentation (pyocanin 82%↓; pyoverdine 48%↑), exopolysaccharide synthesis (76%↑) and biofilm formation, susceptibility to antibiotics (streptomycin and augmentin), protein synthesis and export (65%↑), nitrogen metabolism (37%↑ nitrite accumulation), and siderophore production in this pathogen. Network analysis of the differentially expressed genes in the transcriptome of the silversol-treated bacterium identified ten genes as the potential molecular targets: norB, norD, nirS, nirF, nirM, nirQ, nosZ, nosY, narK1, and norE (all associated with nitrogen metabolism or denitrification). Three of them (norB, narK1, and norE) were also validated through RT-PCR.

CONCLUSIONS

Generation of nitrosative stress and disturbance of iron homeostasis were found to be the major mechanisms associated with anti-Pseudomonas activity of Silversol®.

摘要

背景

铜绿假单胞菌是一种臭名昭著的病原体。其多药耐药株被列为优先病原体之一,急需发现新的抗菌药物,并阐明新的抗致病性机制。本研究描述了胶体纳米银制剂 Silversol®对多药耐药铜绿假单胞菌的多种抗菌作用。

结果

发现 Silversol®对铜绿假单胞菌的最小抑菌浓度(MIC)为 1.5ppm;在亚 MIC(1ppm)下,它能够改变群体感应调节的色素沉着(减少 82%的吡咯烷酮 82%;增加 48%的绿脓菌素)、外多糖合成(增加 76%)和生物膜形成、对抗生素(链霉素和氨曲南)的敏感性、蛋白质合成和外排(增加 65%)、氮代谢(亚硝酸盐积累增加 37%)和铁载体的产生。对 Silversol 处理细菌的转录组中差异表达基因的网络分析鉴定了十个潜在的分子靶标基因:norB、norD、nirS、nirF、nirM、nirQ、nosZ、nosY、narK1 和 norE(均与氮代谢或反硝化有关)。其中三个(norB、narK1 和 norE)也通过 RT-PCR 进行了验证。

结论

产生硝化应激和扰乱铁稳态被发现是与 Silversol®抗铜绿假单胞菌活性相关的主要机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3232/10591374/68dd8c77fff0/12866_2023_3062_Fig1_HTML.jpg

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