title: Anaplasma phagocytophilumInfection Subverts Carbohydrate Metabolic Pathways in the Tick Vector,Ixodes scapularis.
abstract: The obligate intracellular pathogen,Anaplasma phagocytophilum, is the causative agent of human, equine, and canine granulocytic anaplasmosis and tick-borne fever (TBF) in ruminants.A. phagocytophilumhas become an emerging tick-borne pathogen in the United States, Europe, Africa, and Asia, with increasing numbers of infected people and animals every year. It has been recognized that intracellular pathogens manipulate host cell metabolic pathways to increase infection and transmission in both vertebrate and invertebrate hosts. However, our current knowledge on howA. phagocytophilumaffect these processes in the tick vector,Ixodes scapularisis limited. In this study, a genome-wide search for components of major carbohydrate metabolic pathways was performed inI. scapularisticks for which the genome was recently published. The enzymes involved in the seven major carbohydrate metabolic pathways glycolysis, gluconeogenesis, pentose phosphate, tricarboxylic acid cycle (TCA), glyceroneogenesis, and mitochondrial oxidative phosphorylation and β-oxidation were identified. Then, the available transcriptomics and proteomics data was used to characterize the mRNA and protein levels ofI. scapularismajor carbohydrate metabolic pathway components in response toA. phagocytophiluminfection of tick tissues and cultured cells. The results showed that major carbohydrate metabolic pathways are conserved in ticks.A. phagocytophiluminfection inhibits gluconeogenesis and mitochondrial metabolism, but increases the expression of glycolytic genes. A model was proposed to explain howA. phagocytophilumcould simultaneously control tick cell glucose metabolism and cytoskeleton organization, which may be achieved in part by up-regulating and stabilizing hypoxia inducible factor 1 alpha in a hypoxia-independent manner. The present work provides a more comprehensive view of the major carbohydrate metabolic pathways involved in the response toA. phagocytophiluminfection in ticks, and provides the basis for further studies to develop novel strategies for the control of granulocytic anaplasmosis.
authors.affiliation: Institute of Parasitology, Biology Center, Czech Academy of SciencesCeské Budejovice, Czechia; Faculty of Science, University of South BohemiaCeské Budejovice, Czechia.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Cabezas-Cruz
authors.affiliation: SaBio. Instituto de Investigación en Recursos Cinegéticos (CSIC-UCLM-JCCM) Ciudad Real, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Alberdi
authors.affiliation: Institute of Parasitology, Biology Center, Czech Academy of SciencesCeské Budejovice, Czechia; Department of Virology, Veterinary Research InstituteBrno, Czechia.
authors.forename: James J
authors.initials: JJ
authors.lastname: Valdés
authors.affiliation: SaBio. Instituto de Investigación en Recursos Cinegéticos (CSIC-UCLM-JCCM) Ciudad Real, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Villar
authors.affiliation: SaBio. Instituto de Investigación en Recursos Cinegéticos (CSIC-UCLM-JCCM)Ciudad Real, Spain; Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State UniversityStillwater, OK, USA.
authors.forename: José
authors.initials: J
authors.lastname: de la Fuente
mesh_terms: D041081:Anaplasma phagocytophilum / Q000472:pathogenicity / Q000502:physiology; D000712:Anaplasmosis / Q000378:metabolism*; D000818:Animals; D060829:Arthropod Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D050260:Carbohydrate Metabolism / Q000235:genetics*; D002241:Carbohydrates; D002460:Cell Line; D002952:Citric Acid Cycle / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D005943:Gluconeogenesis / Q000235:genetics; D006019:Glycolysis / Q000235:genetics; D054884:Host-Pathogen Interactions / Q000235:genetics*; D018884:Ixodes / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism* / Q000382:microbiology; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D010427:Pentose Phosphate Pathway / Q000235:genetics; D017434:Protein Structure, Tertiary; D040901:Proteomics / Q000379:methods; D012469:Salivary Glands / Q000382:microbiology; D059467:Transcriptome / Q000235:genetics
chemical_list: D060829:Arthropod Proteins; D002241:Carbohydrates
keywords: Anaplasma phagocytophilum; Ixodes scapularis; glucose metabolism; proteomics; transcriptomics