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膳食矿物质对……毒力特性的影响

Effect of Dietary Minerals on Virulence Attributes of .

作者信息

Bhattaram Varunkumar, Upadhyay Abhinav, Yin Hsin-Bai, Mooyottu Shankumar, Venkitanarayanan Kumar

机构信息

Department of Animal Science, University of Connecticut, StorrsCT, United States.

Department of Poultry Science, University of Arkansas, FayettevilleAR, United States.

出版信息

Front Microbiol. 2017 May 19;8:911. doi: 10.3389/fmicb.2017.00911. eCollection 2017.

Abstract

is a water-borne pathogen responsible for causing a toxin-mediated profuse diarrhea in humans, leading to severe dehydration and death in unattended patients. With increasing reports of antibiotic resistance in , there is a need for alternate interventional strategies for controlling cholera. A potential new strategy for treating infectious diseases involves targeting bacterial virulence rather than growth, where a pathogen's specific mechanisms critical for causing infection in hosts are inhibited. Since bacterial motility, intestinal colonization and cholera toxin are critical components in pathogenesis, attenuating these virulence factors could potentially control cholera in humans. In this study, the efficacy of sub-inhibitory concentration (SIC, highest concentration not inhibiting bacterial growth) of essential minerals, zinc (Zn), selenium (Se), and manganese (Mn) in reducing motility and adhesion to intestinal epithelial cells (Caco-2), cholera toxin production, and toxin binding to the ganglioside receptor (GM1) was investigated. Additionally, attachment and toxin production in an mouse intestine model was determined. Further, the effect of Zn, Se and Mn on virulence genes, (toxin production), (motility), (intestinal colonization), and (master regulon) was determined using real-time quantitative PCR. All three minerals significantly reduced motility, adhesion to Caco-2 cells, and cholera toxin production , and decreased adhesion and toxin production in mouse intestine ( < 0.05). In addition, Zn, Se, and Mn down-regulated the transcription of virulence genes, , and Results suggest that Zn, Se, and Mn could be potentially used to reduce virulence. However, studies in an animal model are necessary to validate these results.

摘要

是一种水传播病原体,可导致人类出现毒素介导的大量腹泻,在未得到治疗的患者中会导致严重脱水和死亡。随着关于抗生素耐药性的报道不断增加,需要有替代的干预策略来控制霍乱。一种潜在的治疗传染病的新策略是针对细菌毒力而非生长进行靶向治疗,即抑制病原体在宿主中引起感染的特定关键机制。由于细菌运动性、肠道定植和霍乱毒素是霍乱发病机制中的关键组成部分,减弱这些毒力因子可能潜在地控制人类霍乱。在本研究中,研究了必需矿物质锌(Zn)、硒(Se)和锰(Mn)的亚抑制浓度(SIC,不抑制细菌生长的最高浓度)在降低霍乱弧菌运动性、对肠上皮细胞(Caco-2)的黏附、霍乱毒素产生以及毒素与神经节苷脂受体(GM1)结合方面的功效。此外,还测定了霍乱弧菌在小鼠肠道模型中的黏附和毒素产生情况。进一步地,使用实时定量PCR测定了Zn、Se和Mn对霍乱弧菌毒力基因、(毒素产生)、(运动性)、(肠道定植)和(主调控子)的影响。所有这三种矿物质均显著降低了霍乱弧菌的运动性、对Caco-2细胞的黏附以及霍乱毒素产生,并减少了小鼠肠道中霍乱弧菌的黏附和毒素产生(<0.05)。此外,Zn、Se和Mn下调了毒力基因、和的转录。结果表明,Zn、Se和Mn可能潜在地用于降低霍乱弧菌的毒力。然而,需要在动物模型中进行进一步研究以验证这些结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7294/5437166/5dddadc4a7fe/fmicb-08-00911-g001.jpg

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