Carbohydrate Metabolic Compensation Coupled to High Tolerance to Oxidative Stress in Ticks

Abstract

Reactive oxygen species (ROS) are natural byproducts of metabolism that have toxic effects well documented in mammals. In hematophagous arthropods, however, these processes are not largely understood. Here, we describe that Rhipicephalus microplus ticks and embryonic cell line (BME26) employ an adaptive metabolic compensation mechanism that confers tolerance to hydrogen peroxide (H2O2) at concentrations too high for others organisms. Tick survival and reproduction are not affected by H2O2 exposure, while BME26 cells morphology was only mildly altered by the treatment. Furthermore, H2O2-tolerant BME26 cells maintained their proliferative capacity unchanged. We evaluated several genes involved in gluconeogenesis, glycolysis, and pentose phosphate pathway, major pathways for carbohydrate catabolism and anabolism, describing a metabolic mechanism that explains such tolerance. Genetic and catalytic control of the genes and enzymes associated with these pathways are modulated by glucose uptake and energy resource availability. Transient increase in ROS levels, oxygen consumption, and ROS-scavenger enzymes, as well as decreased mitochondrial superoxide levels, were indicative of cell adaptation to high H2O2 exposure, and suggested a tolerance strategy developed by BME26 cells to cope with oxidative stress. Moreover, NADPH levels increased upon H2O2 challenge, and this phenomenon was sustained mainly by G6PDH activity. Interestingly, G6PDH knockdown in BME26 cells did not impair H2O2 tolerance, but generated an increase in NADP-ICDH transcription. In agreement with the hypothesis of a compensatory NADPH production in these cells, NADP-ICDH knockdown increased G6PDH relative transcript level. The present study unveils the first metabolic evidence of an adaptive mechanism to cope with high H2O2 exposure and maintain redox balance in ticks.

Large-Scale Comparative Analyses of Tick Genomes Elucidate Their Genetic Diversity and Vector Capacities

“…We performed orthology analysis for our six genomes and I. scapularis (Miller et al, 2018) genome. First, the protein sequences of gene families with various functions, including iron metabolism, carbohydrate metabolism, amino acid metabolism, chemosensory functions, gustatory functions, immune functions, heme and hemoglobin digestion, detoxification of xenobiotic factors, opsin-related functions, lipid metabolism, oxidative stress, purine metabolism, and mechanosensation, were retrieved and divided into subgroups according to their specific functions Antunes et al, 2012;Bohbot et al, 2014;Cabezas-Cruz et al, 2017;Della Noce et al, 2019;Eyun et al, 2017;Galay et al, 2013;Graç a-Souza et al, 2002Gulia-Nuss et al, 2016;Hajdusek et al, 2009Hajdusek et al, , 2013Hajdusek et al, , 2016Horn et al, 2009;International Glossina Genome Initiative, 2014;Iovinella et al, 2016;Josek et al, 2018;Liu et al, 2011Liu et al, , 2012Merino et al, 2011;Pal et al, 2004;Perner et al, 2016;Salem et al, 2014;Sanders et al, 2003;Sonenshine and Macaluso, 2017;Sultana et al, 2010;Weisheit et al, 2015;Whiten et al, 2018;Winzerling and Pham, 2006). The gene families in each subgroup are shown in Table S3.…”

Tick and Host Derived Compounds Detected in the Cement Complex Substance

“…In addition to tick and host derived proteins, chemical composition may be affected by cofactors such as nicotinamide adenine dinucleotide phosphate (NADPH; C 21 H 26 N 7 O 17 P 3 ). Reduced NAPDH is an essential electron donor that provides the reducing power regulating multiple anabolic reactions, including those responsible for the biosynthesis of all major cell components in all organisms including ticks [60][61][62]. Increased levels of NADPH in ticks have been associated with response to Anaplasma phagocytophilum pathogen infection and tolerance to oxidative stress [61,62].…”

“…Reduced NAPDH is an essential electron donor that provides the reducing power regulating multiple anabolic reactions, including those responsible for the biosynthesis of all major cell components in all organisms including ticks [60][61][62]. Increased levels of NADPH in ticks have been associated with response to Anaplasma phagocytophilum pathogen infection and tolerance to oxidative stress [61,62]. The source of other chemical elements such as Na, K, Cl, and P, which may contribute to cement biomineralization and coating [29,63] probably come from environmental sources (e.g., water, air, and soil).…”

Redox imbalance induces remodeling of glucose metabolism in Rhipicephalus microplus embryonic cell line

“…Metabolic changes are increasingly recognized as important drivers of malignancy, and cancer-specific metabolic alterations are becoming an important research theme. Arthropods have been broadly used to study how metabolism is orchestrated to support biological processes, including growth, proliferation, and differentiation in normal development (5,23,(29)(30)(31). The fact that these organisms share a gene conservation with humans and use similar metabolic J o u r n a l P r e -p r o o f reprogramming strategies can make them a valuable tool for comparative analysis with cancer metabolism.…”