色氨酸衍生物5 -羟色胺和吲哚对肠道病原体毒力调节的组合作用。

IF 4.7 1区 生物学 Q1 MICROBIOLOGY
mBio Pub Date : 2025-10-08 Epub Date: 2025-08-25 DOI:10.1128/mbio.02067-25
Mehmet Ali Hoskan, Vanessa Sperandio
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引用次数: 0

摘要

人类肠道中存在丰富的信号,介导宿主-微生物群的交流,并与肠道-脑轴相交。色氨酸衍生物5 -羟色胺和吲哚在肠道中的空间定位存在差异,这是肠道病原体寻找定殖生态位的重要线索。这两种信号都可以被肠出血性大肠杆菌(EHEC)和啮齿柠檬酸杆菌(一种被广泛用作EHEC替代动物模型的小鼠病原体)等肠道病原体感知。肠出血性大肠杆菌和啮齿c的毒力决定因素包括肠细胞附着和消退(AE)病变形成所必需的基因,这些基因包含在肠细胞消退(LEE)致病性岛位点内。这两种信号在体外和哺乳动物感染期间抑制LEE的表达。吲哚和5 -羟色胺在毒力中的作用已经分别被初步研究。在这里,我们展示了这些信号在体外和小鼠感染期间对细菌毒力相互拮抗的组合效应。这两种信号在体内的作用是通过药理学和遗传策略来控制小鼠的血清素水平,通过抑制血清素再摄取转运体(SERT)来增加肠道中血清素的水平。同时,通过感染产生或不产生吲哚的C. rodentium菌株,或用WT或ΔtnaA(不产生吲哚)拟杆菌(Bacteroides thetaiotaomicron)菌株重新定殖微生物群,吲哚水平发生了变化。单独增加肠道中血清素和吲哚的水平可降低啮齿鼠的发病机制。然而,当这两个信号同时升高时,它们会相互拮抗。重要意义病原体感知肠道内的大量信号,通过在正确的生态位内精确调节毒力基因表达,成功地建立定植。我们的研究表明,重要的是不要忽视不同信号机制的相互作用,以了解肠道病原体毒力调节的复杂性。尽管5 -羟色胺和吲哚都是具有相似结构的色氨酸衍生物,各自都能降低细菌的毒力,但对这两种信号的组合感知会抵消彼此的影响。了解这些感知机制可以更好地了解针对肠道感染的潜在治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Combinatorial effects of tryptophan derivatives serotonin and indole on virulence modulation of enteric pathogens.

There is a wealth of signals present in the human gut that mediate host-microbiota communication and intersect with the gut-brain-axis. There is differential spatial localization of the tryptophan derivatives serotonin and indole in the gut, which are important cues for enteric pathogens to find their colonization niche. Both signals are sensed by enteric pathogens such as enterohemorrhagic Escherichia coli (EHEC) and Citrobacter rodentium, a murine pathogen extensively employed as a surrogate animal model for EHEC. EHEC and C. rodentium virulence determinants include genes necessary for the attaching and effacing (AE) lesion formation on enterocytes, which are contained within the locus of enterocyte effacement (LEE) pathogenicity island. Both signals inhibit LEE expression in vitro and during mammalian infection. The roles of indole and serotonin in virulence have been initially interrogated separately. Here, we show the combinatorial effect of these signals antagonizing each other's activity on bacterial virulence in vitro and during murine infection. The role of both signals in vivo was interrogated by manipulating the serotonin levels in mice through pharmacological and genetic strategies to increase the levels of serotonin in the gut by inhibiting the serotonin reuptake transporter (SERT). Simultaneously, indole levels were altered through infection with C. rodentium strains that either produce or don't indole or recolonizing the microbiota with WT or ΔtnaA (does not produce indole) strains of Bacteroides thetaiotaomicron. Individually increasing the levels of serotonin and indole in the gut decreased C. rodentium pathogenesis. However, when both signals were elevated simultaneously, they antagonized each other's activity.IMPORTANCEPathogens sense a plethora of signals within the gut to successfully establish colonization by precise regulation of virulence gene expression within the right niche. Our study shows that it is crucial to not disregard the interaction of different signaling mechanisms to understand the complexity of virulence regulation in enteric pathogens. Even though serotonin and indole are both tryptophan derivatives with similar structures that individually decrease bacterial virulence, combinatorial sensing of these two signals cancels out each other's effect. Understanding these sensing mechanisms provides a better insight into potential therapeutic approaches against enteric infections.

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来源期刊
mBio
mBio MICROBIOLOGY-
CiteScore
10.50
自引率
3.10%
发文量
762
审稿时长
1 months
期刊介绍: mBio® is ASM''s first broad-scope, online-only, open access journal. mBio offers streamlined review and publication of the best research in microbiology and allied fields.
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