Ixodes scapularis Tick Cells Control Anaplasma phagocytophilum Infection by Increasing the Synthesis of Phosphoenolpyruvate from Tyrosine.
Ixodes scapularis Tick Cells Control Anaplasma phagocytophilum Infection by Increasing the Synthesis of Phosphoenolpyruvate from Tyrosine.
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DOI：
10.3389/fcimb.2017.00375
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发表时间：
2017
影响因子：
5.7
通讯作者：
de la Fuente J
中科院分区：
文献类型：
--
作者：
Cabezas-Cruz A;Espinosa PJ;Obregón DA;Alberdi P;de la Fuente J
专性细胞内病原体，嗜吞噬细胞无形体，是人类和动物中危及生命的疾病的病原体。A.在美国、欧洲、非洲和亚洲，嗜吞噬细胞菌是一种新出现的蜱传病原体，感染的人和动物的数量每年都在增加。越来越多的人认识到，细胞内病原体改变宿主细胞代谢途径，以增加脊椎动物和无脊椎动物宿主中的感染和传播。最近的报道表明，氨基酸是宿主-病原体代谢相互作用的中心。在这项研究中，氨基酸代谢途径的组成部分，肩突硬蜱，主要蜱媒介的A。嗜吞噬细胞菌在美国，其基因组最近公布。鉴定了参与20种氨基酸合成和降解途径的酶。然后，利用现有的转录组学和蛋白质组学数据来表征I.肩胛肌氨基酸代谢途径组分对A.蜱组织和ISE 6蜱细胞的嗜吞噬细胞菌感染。我们的分析集中在碳水化合物和氨基酸代谢之间的相互作用，在A。嗜吞噬细胞菌感染的ISE 6细胞。结果表明，蜱细胞增加了磷酸烯醇式丙酮酸（PEP）的合成，从酪氨酸到对照A。嗜吞噬细胞菌感染代谢途径分析表明，这是通过以下方式实现的：（i）增加线粒体磷酸烯醇丙酮酸羧激酶（PEPCK-M）的转录物和蛋白质水平，（ii）将酪氨酸分流到三羧酸（TCA）循环中以增加富马酸和草酰乙酸，富马酸和草酰乙酸将被PEPCK-M转化为PEP，以及（iii）阻断使用PEP下游代谢的所有途径（即，从头丝氨酸合成途径（SSP）、甘油生成和甘油异生）。虽然隔离宿主PEP可能对这种细菌至关重要，因为它不能主动进行糖酵解以产生PEP，但过量的这种代谢物可能对A.嗜吞噬细胞菌目前的工作提供了一个更全面的观点，主要的氨基酸代谢途径参与蜱病原体感染的反应，并提供了基础，为进一步研究，以开发新的战略控制粒细胞无形体病。
The obligate intracellular pathogen, Anaplasma phagocytophilum, is the causative agent of life-threatening diseases in humans and animals. A. phagocytophilum is an emerging tick-borne pathogen in the United States, Europe, Africa and Asia, with increasing numbers of infected people and animals every year. It is increasingly recognized that intracellular pathogens modify host cell metabolic pathways to increase infection and transmission in both vertebrate and invertebrate hosts. Recent reports have shown that amino acids are central to the host–pathogen metabolic interaction. In this study, a genome-wide search for components of amino acid metabolic pathways was performed in Ixodes scapularis, the main tick vector of A. phagocytophilum in the United States, for which the genome was recently published. The enzymes involved in the synthesis and degradation pathways of the twenty amino acids were identified. Then, the available transcriptomics and proteomics data was used to characterize the mRNA and protein levels of I. scapularis amino acid metabolic pathway components in response to A. phagocytophilum infection of tick tissues and ISE6 tick cells. Our analysis was focused on the interplay between carbohydrate and amino acid metabolism during A. phagocytophilum infection in ISE6 cells. The results showed that tick cells increase the synthesis of phosphoenolpyruvate (PEP) from tyrosine to control A. phagocytophilum infection. Metabolic pathway analysis suggested that this is achieved by (i) increasing the transcript and protein levels of mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M), (ii) shunting tyrosine into the tricarboxylic acid (TCA) cycle to increase fumarate and oxaloacetate which will be converted into PEP by PEPCK-M, and (iii) blocking all the pathways that use PEP downstream gluconeogenesis (i.e., de novo serine synthesis pathway (SSP), glyceroneogenesis and gluconeogenesis). While sequestering host PEP may be critical for this bacterium because it cannot actively carry out glycolysis to produce PEP, excess of this metabolite may be toxic for A. phagocytophilum. The present work provides a more comprehensive view of the major amino acid metabolic pathways involved in the response to pathogen infection in ticks, and provides the basis for further studies to develop novel strategies for the control of granulocytic anaplasmosis.
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影响因子：
4.5
作者：
Dunning Hotopp JC;Lin M;Madupu R;Crabtree J;Angiuoli SV;Eisen JA;Seshadri R;Ren Q;Wu M;Utterback TR;Smith S;Lewis M;Khouri H;Zhang C;Niu H;Lin Q;Ohashi N;Zhi N;Nelson W;Brinkac LM;Dodson RJ;Rosovitz MJ;Sundaram J;Daugherty SC;Davidsen T;Durkin AS;Gwinn M;Haft DH;Selengut JD;Sullivan SA;Zafar N;Zhou L;Benahmed F;Forberger H;Halpin R;Mulligan S;Robinson J;White O;Rikihisa Y;Tettelin H
通讯作者：
Tettelin H
影响因子：
9.8
作者：
Leitão-Gonçalves R;Carvalho-Santos Z;Francisco AP;Fioreze GT;Anjos M;Baltazar C;Elias AP;Itskov PM;Piper MDW;Ribeiro C
通讯作者：
Ribeiro C
影响因子：
16.6
作者：
Gulia-Nuss M;Nuss AB;Meyer JM;Sonenshine DE;Roe RM;Waterhouse RM;Sattelle DB;de la Fuente J;Ribeiro JM;Megy K;Thimmapuram J;Miller JR;Walenz BP;Koren S;Hostetler JB;Thiagarajan M;Joardar VS;Hannick LI;Bidwell S;Hammond MP;Young S;Zeng Q;Abrudan JL;Almeida FC;Ayllón N;Bhide K;Bissinger BW;Bonzon-Kulichenko E;Buckingham SD;Caffrey DR;Caimano MJ;Croset V;Driscoll T;Gilbert D;Gillespie JJ;Giraldo-Calderón GI;Grabowski JM;Jiang D;Khalil SMS;Kim D;Kocan KM;Koči J;Kuhn RJ;Kurtti TJ;Lees K;Lang EG;Kennedy RC;Kwon H;Perera R;Qi Y;Radolf JD;Sakamoto JM;Sánchez-Gracia A;Severo MS;Silverman N;Šimo L;Tojo M;Tornador C;Van Zee JP;Vázquez J;Vieira FG;Villar M;Wespiser AR;Yang Y;Zhu J;Arensburger P;Pietrantonio PV;Barker SC;Shao R;Zdobnov EM;Hauser F;Grimmelikhuijzen CJP;Park Y;Rozas J;Benton R;Pedra JHF;Nelson DR;Unger MF;Tubio JMC;Tu Z;Robertson HM;Shumway M;Sutton G;Wortman JR;Lawson D;Wikel SK;Nene VM;Fraser CM;Collins FH;Birren B;Nelson KE;Caler E;Hill CA
通讯作者：
Hill CA
影响因子：
3.1
作者：
Hondalus, MK;Bardarov, S;Bloom, BR
通讯作者：
Bloom, BR
影响因子：
3.7
作者：
Cabezas-Cruz, Alejandro;Alberdi, Pilar;de la Fuente, Jose
通讯作者：
de la Fuente, Jose