Arthropod-borne pathogens are responsible for hundreds of millions of infections in humans each year. The blacklegged tick, Ixodes scapularis, is the predominant arthropod vector in the United States and is responsible for transmitting several human pathogens, including the Lyme disease spirochete Borrelia burgdorferi and the obligate intracellular rickettsial bacterium Anaplasma phagocytophilum, which causes human granulocytic anaplasmosis. However, tick metabolic response to microbes and whether metabolite allocation occurs upon infection remain unknown. Here we investigated metabolic reprogramming in the tick ectoparasite I. scapularis and determined that the rickettsial bacterium A. phagocytophilum and the spirochete B. burgdorferi induced glycolysis in tick cells. Surprisingly, the endosymbiont Rickettsia buchneri had a minimal effect on bioenergetics. An unbiased metabolomics approach following A. phagocytophilum infection of tick cells showed alterations in carbohydrate, lipid, nucleotide and protein metabolism, including elevated levels of the pleiotropic metabolite β-aminoisobutyric acid. We manipulated the expression of genes associated with β-aminoisobutyric acid metabolism in I. scapularis, resulting in feeding impairment, diminished survival and reduced bacterial acquisition post haematophagy. Collectively, we discovered that metabolic reprogramming affects interspecies relationships and fitness in the clinically relevant tick I. scapularis.

节肢动物传播的病原体每年导致数亿人感染。黑腿蜱，肩胛硬蜱，是美国主要的节肢动物媒介，负责传播多种人类病原体，包括莱姆病螺旋体伯氏疏螺旋体和专性细胞内立克次体细菌嗜吞噬细胞无形体，后者会导致人类粒细胞无形体病。然而，蜱对微生物的代谢反应以及感染后是否发生代谢分配仍然未知。在这里，我们研究了蜱外寄生虫I. scapularis中的代谢重编程，并确定立克次体细菌A. phagocytophilum和螺旋体B. burgdorferi诱导蜱细胞中的糖酵解。令人惊讶的是，内共生体布氏立克次体对生物能学的影响很小。蜱细胞感染嗜吞噬细胞 A.后的无偏代谢组学方法显示碳水化合物、脂质、核苷酸和蛋白质代谢发生变化，包括多效性代谢物 β-氨基异丁酸水平升高。我们操纵了肩胛I. scapularis中与 β-氨基异丁酸代谢相关的基因的表达，导致摄食障碍、存活率降低以及吸血后细菌获得减少。总的来说，我们发现代谢重编程会影响临床相关肩胛蜱的种间关系和适应性。