Peixoto Rafael J M, Alves Eduardo S, Wang Melody, Ferreira Rosana B R, Granato Alessandra, Han Jun, Gill Hira, Jacobson Kevan, Lobo Leandro A, Domingues Regina M C P, Borchers Christoph H, Davies Julian E, Finlay B Brett, Antunes L Caetano M
Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Michael Smith Laboratories, The University of British Columbia, Vancouver, Canada.
Appl Environ Microbiol. 2017 Sep 15;83(19). doi: 10.1128/AEM.01148-17. Print 2017 Oct 1.
The human microbiome is a collection of microorganisms that inhabit every surface of the body that is exposed to the environment, generally coexisting peacefully with their host. These microbes have important functions, such as producing vitamins, aiding in maturation of the immune system, and protecting against pathogens. We have previously shown that a small-molecule extract from the human fecal microbiome has a strong repressive effect on serovar Typhimurium host cell invasion by modulating the expression of genes involved in this process. Here, we describe the characterization of this biological activity. Using a series of purification methods, we obtained fractions with biological activity and characterized them by mass spectrometry. These experiments revealed an abundance of aromatic compounds in the bioactive fraction. Selected compounds were obtained from commercial sources and tested with respect to their ability to repress the expression of , the gene encoding the master regulator of invasion genes in We found that the aromatic compound 3,4-dimethylbenzoic acid acts as a strong inhibitor of expression and of invasion of cultured host cells by Future studies should reveal the molecular details of this phenomenon, such as the signaling cascades involved in sensing this bioactive molecule. Microbes constantly sense and adapt to their environment. Often, this is achieved through the production and sensing of small extracellular molecules. The human body is colonized by complex communities of microbes, and, given their biological and chemical diversity, these ecosystems represent a platform where the production and sensing of molecules occur. In previous work, we showed that small molecules produced by microbes from the human gut can significantly impair the virulence of the enteric pathogen Here, we describe a specific compound from the human gut that produces this same effect. The results from this work not only shed light on an important biological phenomenon occurring in our bodies but also may represent an opportunity to develop drugs that can target these small-molecule interactions to protect us from enteric infections and other diseases.
人类微生物组是指栖息在人体暴露于外界环境的各个表面的微生物集合，它们通常与宿主和平共处。这些微生物具有重要功能，如产生维生素、协助免疫系统成熟以及抵御病原体。我们之前已经表明，从人类粪便微生物组中提取的小分子提取物通过调节参与该过程的基因表达，对鼠伤寒血清型沙门氏菌侵袭宿主细胞具有强烈的抑制作用。在此，我们描述这种生物活性的特征。通过一系列纯化方法，我们获得了具有生物活性的组分，并通过质谱对其进行了表征。这些实验揭示了生物活性组分中存在大量芳香族化合物。从商业来源获得了选定的化合物，并测试了它们抑制鼠伤寒血清型沙门氏菌中侵袭基因主调控因子编码基因表达的能力。我们发现芳香族化合物3,4 - 二甲基苯甲酸是鼠伤寒血清型沙门氏菌表达以及侵袭培养的宿主细胞的强力抑制剂。未来的研究应揭示这一现象的分子细节，例如参与感知这种生物活性分子的信号级联反应。微生物不断感知并适应其环境。通常，这是通过产生和感知细胞外小分子来实现的。人体被复杂的微生物群落定殖，鉴于它们的生物学和化学多样性，这些生态系统代表了一个分子产生和感知发生的平台。在之前的工作中，我们表明人类肠道微生物产生的小分子可显著损害肠道病原体的毒力。在此，我们描述了一种来自人类肠道的产生相同效果的特定化合物。这项工作的结果不仅揭示了我们体内发生的一种重要生物学现象，还可能代表了一个开发能够靶向这些小分子相互作用以保护我们免受肠道感染和其他疾病的药物机会。
