Thiamine Acquisition Strategies Impact Metabolism and Competition in the Gut Microbe Bacteroides thetaiotaomicron
Thiamine Acquisition Strategies Impact Metabolism and Competition in the Gut Microbe Bacteroides thetaiotaomicron
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DOI：
10.1128/msystems.00116-17
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发表时间：
2017-09-01
期刊：
影响因子：
6.4
通讯作者：
Degnan, Patrick H.
中科院分区：
文献类型：
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作者：
Costliow, Zachary A.;Degnan, Patrick H.
硫胺素(维生素B-1)是所有生物体必需的辅因子。人类主要通过饮食获得硫胺素，硫胺素缺乏会对神经系统产生不利影响。然而，肠道微生物在调节硫胺素利用率方面所起的作用却知之甚少，关于硫胺素如何影响微生物肠道群落的稳定性也知之甚少。为了研究硫胺素在肠道中的作用，我们使用了模式肠道微生物类杆菌。转录组测序(RNA-seq)显示，当硫胺素存在时，硫胺素和氨基酸的生物合成、糖酵解和嘌呤代谢的全球下调。利用硫胺素生物合成和转运基因突变的遗传突变体，我们确定这两个系统对硫胺素缺乏的培养基中的生长都是关键的。双运输突变体的缺陷表明硫胺转运和生物合成之间存在一种未知的反馈机制。突变表型在成对竞争中被概括，强调了当硫胺浓度变化时编码多种多样的硫胺获取机制的重要性。此外，液-质联用分析证实，外源硫胺素水平会影响白背飞虱体内的硫胺素库。此外，我们通过计算检查了其他肠道微生物获取硫胺素的能力，并确定了不同血统的硫胺素获取策略的差异。在类杆菌中，硫胺素的运输能力和生物合成能力是共同的。综上所述，这些数据表明，B.thetaotaomicron使用的硫胺获取机制不仅对其生理和健康至关重要，而且还提供了建模其他肠道微生物如何响应肠道中硫胺可用性变化的机会。重要的是，肠道微生物运输、合成和竞争维生素B-1(硫胺素)的能力的变化预计将影响微生物区系的结构和稳定性，最终这种变化可能对人类健康产生直接和间接的影响。我们的研究确定了肠道拟杆菌获取硫胺的不同策略。我们展示了在竞争环境中硫胺素生物合成或运输的存在或不存在如何显著影响B.thetaiotaomicron的丰度。这项研究进一步证明，改变硫胺素等水溶性维生素的存在或浓度可能是控制肠道群落组成的有效方法。反过来，有针对性的硫胺素输送可以用于治疗，以改变与疾病相关的反生菌群落。
Thiamine (vitamin B-1) is an essential cofactor for all organisms. Humans primarily acquire thiamine through their diet, and thiamine deficiencies have adverse neurological effects. However, the role gut microbes play in modulating thiamine availability is poorly understood, and little is known about how thiamine impacts the stability of microbial gut communities. To investigate thiamine's role in the gut, we utilized the model gut microbe Bacteroides thetaiotaomicron. Transcriptome sequencing (RNA-seq) revealed a global downregulation of thiamine and amino acid biosynthesis, glycolysis, and purine metabolism when thiamine was present. Using genetic mutants with thiamine biosynthesis and transport locus mutations, we determined both systems were critical for growth in thiamine-deficient medium. The defect in the double transport mutant suggests an uncharacterized feedback mechanism between thiamine transport and biosynthesis in B. thetaiotaomicron. Mutant phenotypes were recapitulated during pairwise competitions, reinforcing the importance of encoding versatile thiamine acquisition mechanisms when thiamine concentrations are variable. In addition, liquid chromatography-mass spectrometry (LCMS) analyses corroborate that exogenous thiamine levels affect the internal thiamine pool of B. thetaiotaomicron. Furthermore, we computationally examined the ability of other gut microbes to acquire thiamine and identified lineage-specific differences in thiamine acquisition strategies. Among the Bacteroidetes, the capacities for both thiamine transport and biosynthesis are common. Together, these data show that thiamine acquisition mechanisms used by B. thetaiotaomicron not only are critical for its physiology and fitness but also provide the opportunity to model how other gut microbes may respond to the shifting availability of thiamine in the gut.IMPORTANCE Variation in the ability of gut microbes to transport, synthesize, and compete for vitamin B-1 (thiamine) is expected to impact the structure and stability of the microbiota, and ultimately this variation may have both direct and indirect effects on human health. Our study identifies the diverse strategies employed by gut Bacteroidetes to acquire thiamine. We demonstrate how the presence or absence of thiamine biosynthesis or transport dramatically affects the abundance of B. thetaiotaomicron in a competitive environment. This study adds further evidence that altering the presence or concentrations of water-soluble vitamins such as thiamine may be an effective method for manipulating gut community composition. In turn, targeted thiamine delivery could be used therapeutically to alter dysbiotic communities linked to disease.