A Tale of Three Species: Adaptation of Sodalis glossinidius to Tsetse Biology, Wigglesworthia Metabolism, and Host Diet
A Tale of Three Species: Adaptation of Sodalis glossinidius to Tsetse Biology, Wigglesworthia Metabolism, and Host Diet
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DOI：
10.1128/mbio.02106-18
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发表时间：
2019-01-01
期刊：
影响因子：
6.4
通讯作者：
Thomas, Gavin H.
中科院分区：
文献类型：
--
作者：
Hall, Rebecca J.;Flanagan, Lindsey A.;Thomas, Gavin H.
采采蝇是布氏锥虫的昆虫媒介，布氏锥虫是非洲人类锥虫病的病原体。锥虫的定植和传播与一种次生共生细菌——光泽度梭菌的存在呈正相关。我们对这种细菌的代谢需求和与宿主的相互作用了解甚少，在此我们描述了一种s.b axininidius代谢模型。该模型能够设计和实验验证一种支持S.舌鱼体外生长的定义培养基。这随后被用于分析S.舌藻代谢的体外方面，揭示了共生体对其环境的多种独特适应。对糖的持续依赖，以及几丁质单体n -乙酰-d -氨基葡萄糖作为碳和能量来源的重要性，表明了对宿主衍生分子的适应。对富含氨基酸的血液饮食的适应揭示了对l -谷氨酸作为碳和氮的来源的强烈依赖，以及通过挽救预测的l -精氨酸营养不良的能力。最后，硫胺素生物合成的选择性丧失，一种由初级共生体Wigglesworthia gloss india提供给宿主的维生素，揭示了共生体间的依赖。为了利用环境衍生的代谢物而进行的还原性进化导致了代谢网络中的多个弱点。这些弱点可能成为抑制光泽度葡萄球菌生长和帮助减少锥虫传播的试剂的目标。非洲人类锥虫病是由布鲁氏锥虫寄生虫引起的。采采蝇媒介因其预防疾病传播的潜力而引起人们的兴趣，因为它对布氏体绦虫生命周期的进展和传播至关重要。采采蝇的互利共生内共生体舌索菌与锥虫的建立有关，提供了疾病控制的靶点。在这里，我们描述了一个新的，实验验证的模型的s.s舌的代谢。该模型使一种已定义的生长培养基得以开发，该培养基已成功地用于测试S.舌藻代谢的各个方面。我们认为舌蝇是唯一适应采采蝇生活的，通过它对血液饮食和宿主来源的糖的依赖。此外，舌蝇通过清除舌蝇为舌蝇产生的一种维生素，适应了舌蝇的专性共生体舌蝇。这项工作强调了利用代谢模型来设计共生细菌的生长培养基，并可能提供新的抑制靶点来阻断锥虫的传播。
The tsetse fly is the insect vector for the Trypanosoma brucei parasite, the causative agent of human African trypanosomiasis. The colonization and spread of the trypanosome correlate positively with the presence of a secondary symbiotic bacterium, Sodalis glossinidius. The metabolic requirements and interactions of the bacterium with its host are poorly understood, and herein we describe a metabolic model of S. glossinidius metabolism. The model enabled the design and experimental verification of a defined medium that supports S. glossinidius growth ex vivo. This has been used subsequently to analyze in vitro aspects of S. glossinidius metabolism, revealing multiple unique adaptations of the symbiont to its environment. Continued dependence on a sugar, and the importance of the chitin monomer N-acetyl-D-glucosamine as a carbon and energy source, suggests adaptation to host-derived molecules. Adaptation to the amino acid-rich blood diet is revealed by a strong dependence on L-glutamate as a source of carbon and nitrogen and by the ability to rescue a predicted L-arginine auxotrophy. Finally, the selective loss of thiamine biosynthesis, a vitamin provided to the host by the primary symbiont Wigglesworthia glossinidia, reveals an intersymbiont dependence. The reductive evolution of S. glossinidius to exploit environmentally derived metabolites has resulted in multiple weaknesses in the metabolic network. These weaknesses may become targets for reagents that inhibit S. glossinidius growth and aid the reduction of trypanosomal transmission.IMPORTANCE Human African trypanosomiasis is caused by the Trypanosoma brucei parasite. The tsetse fly vector is of interest for its potential to prevent disease spread, as it is essential for T. brucei life cycle progression and transmission. The tsetse's mutualistic endosymbiont Sodalis glossinidius has a link to trypanosome establishment, providing a disease control target. Here, we describe a new, experimentally verified model of S. glossinidius metabolism. This model has enabled the development of a defined growth medium that was used successfully to test aspects of S. glossinidius metabolism. We present S. glossinidius as uniquely adapted to life in the tsetse, through its reliance on the blood diet and host-derived sugars. Additionally, S. glossinidius has adapted to the tsetse's obligate symbiont Wigglesworthia glossinidia by scavenging a vitamin it produces for the insect. This work highlights the use of metabolic modeling to design defined growth media for symbiotic bacteria and may provide novel inhibitory targets to block trypanosome transmission.