Samaddar Sourabh, O'Neal Anya J, Marnin Liron, Rolandelli Agustin, Singh Nisha, Wang Xiaowei, Butler L Rainer, Rangghran Parisa, Laukaitis Hanna J, Cabrera Paz Francy E, Fiskum Gary M, Polster Brian M, Pedra Joao H F
Department of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, Maryland 21201, USA.
Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology Research, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.
bioRxiv. 2023 May 26:2023.05.26.542501. doi: 10.1101/2023.05.26.542501.
Arthropod-borne microbes rely on the metabolic state of a host to cycle between evolutionarily distant species. For instance, arthropod tolerance to infection may be due to redistribution of metabolic resources, often leading to microbial transmission to mammals. Conversely, metabolic alterations aids in pathogen elimination in humans, who do not ordinarily harbor arthropod-borne microbes. To ascertain the effect of metabolism on interspecies relationships, we engineered a system to evaluate glycolysis and oxidative phosphorylation in the tick . Using a metabolic flux assay, we determined that the rickettsial bacterium and the Lyme disease spirochete , which are transstadially transmitted in nature, induced glycolysis in ticks. On the other hand, the endosymbiont which is transovarially maintained, had a minimal effect on bioenergetics. Importantly, the metabolite β-aminoisobutyric acid (BAIBA) was elevated during infection of tick cells following an unbiased metabolomics approach. Thus, we manipulated the expression of genes associated with the catabolism and anabolism of BAIBA in and detected impaired feeding on mammals, reduced bacterial acquisition, and decreased tick survival. Collectively, we reveal the importance of metabolism for tick-microbe relationships and unveil a valuable metabolite for fitness.
节肢动物传播的微生物依赖宿主的代谢状态在进化上相距遥远的物种之间循环。例如,节肢动物对感染的耐受性可能是由于代谢资源的重新分配,这通常会导致微生物传播给哺乳动物。相反,代谢改变有助于在通常不携带节肢动物传播微生物的人类中清除病原体。为了确定代谢对种间关系的影响,我们设计了一个系统来评估蜱中的糖酵解和氧化磷酸化。使用代谢通量测定法,我们确定在自然条件下经变态阶段传播的立克次氏体细菌和莱姆病螺旋体在蜱中诱导了糖酵解。另一方面,经卵传递维持的内共生体对生物能量学的影响最小。重要的是,采用无偏向代谢组学方法发现,蜱细胞感染期间代谢物β-氨基异丁酸(BAIBA)升高。因此,我们操纵了蜱中与BAIBA分解代谢和合成代谢相关的基因表达,发现蜱对哺乳动物的取食能力受损、细菌获取减少以及蜱的存活率降低。总体而言,我们揭示了代谢对蜱-微生物关系的重要性,并发现了一种对蜱的适应性有价值的代谢物。