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. phagocytophilum has 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 how A. phagocytophilum affect these processes in the tick vector, Ixodes scapularis is limited. In this study, a genome-wide search for components of major carbohydrate metabolic pathways was performed in I. scapularis ticks 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 of I. scapularis major carbohydrate metabolic pathway components in response to A. phagocytophilum infection of tick tissues and cultured cells. The results showed that major carbohydrate metabolic pathways are conserved in ticks. A. phagocytophilum infection inhibits gluconeogenesis and mitochondrial metabolism, but increases the expression of glycolytic genes. A model was proposed to explain how A. phagocytophilum could 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 to A. phagocytophilum infection in ticks, and provides the basis for further studies to develop novel strategies for the control of granulocytic anaplasmosis.
Highlights
Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae) is an obligate intracellular bacterium mainly transmitted by Ixodes spp. ticks
A total of 79 genes coding for the proteins involved in glycolysis, gluconeogenesis, pentose phosphate pathway (PPP), glyceroneogenesis, tricarboxylic acid cycle (TCA), mitochondrial oxidative phosphorylation (OXPHOS) and β-oxidation were identified in the I. scapularis genome (Table 1)
Pyruvate carboxylase (PC) catalyzes the irreversible carboxylation of pyruvate to form oxaloacetate, which is transformed in phosphoenolpyruvate by the cytoplasmic enzyme phosphoenolpyruvate carboxykinase (PEPCK-C; Berg et al, 2002)
Summary
Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae) is an obligate intracellular bacterium mainly transmitted by Ixodes spp. ticks. This emerging pathogen has been reported in the United States, Europe, Africa, and Asia (de la Fuente et al, 2008; Stuen et al, 2013; Kocan et al, 2015), causing human granulocytic anaplasmosis (HGA), equine and canine granulocytic anaplasmosis and tick-borne fever (TBF) of ruminants (de la Fuente et al, 2008; Stuen et al, 2013; Kocan et al, 2015). These mechanisms include but are not limited to remodeling of the cytoskeleton, inhibition of cell apoptosis, manipulation of the immune response, and modification of cell epigenetics and metabolism (de la Fuente et al, 2016a)
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