Metabolic Signatures of Triatomine Vectors of Trypanosoma cruzi Unveiled by Metabolomics

Abstract

Chagas disease is a trypanosomiasis whose causative agent is the protozoan parasite Trypanosoma cruzi, which is transmitted to humans by hematophagous insects known as triatomines and affects a large proportion of South America. The digestive tract of the insect vectors in which T. cruzi develops constitutes a dynamic environment that affects the development of the parasite. Thus, we set out to investigate the chemical composition of the triatomine intestinal tract through a metabolomics approach. We performed Direct Infusion Fourier Transform Ion Cyclotron Resonance Mass Spectrometry on fecal samples of three triatomine species (Rhodnius prolixus, Triatoma infestans, Panstrongylus megistus) fed with rabbit blood. We then identified groups of metabolites whose frequencies were either uniform in all species or enriched in each of them. By querying the Human Metabolome Database, we obtained putative identities of the metabolites of interest. We found that a core group of metabolites with uniform frequencies in all species represented approximately 80% of the molecules detected, whereas the other 20% varied among triatomine species. The uniform core was composed of metabolites of various categories, including fatty acids, steroids, glycerolipids, nucleotides, sugars, and others. Nevertheless, the metabolic fingerprint of triatomine feces differs depending on the species considered. The variable core was mainly composed of prenol lipids, amino acids, glycerolipids, steroids, phenols, fatty acids and derivatives, benzoic acid and derivatives, flavonoids, glycerophospholipids, benzopyrans, and quinolines. Triatomine feces constitute a rich and varied chemical medium whose constituents are likely to affect T. cruzi development and infectivity. The complexity of the fecal metabolome of triatomines suggests that it may affect triatomine vector competence for specific T. cruzi strains. Knowledge of the chemical environment of T. cruzi in its invertebrate host is likely to generate new ways to understand the factors influencing parasite proliferation as well as methods to control Chagas disease.

Metabolomic profiling reveals a finely tuned, starvation-induced metabolic switch in Trypanosoma cruzi epimastigotes

“…Our results are in agreement with recent findings regarding the metabolic environment in the gut of the insect host where a reduced availability of oxygen implies anaerobic fermentation of glucose and amino acid carbon sources. Interestingly, His is the predominant free amino acid in the triatomine feces (33), which correlates with our results showing that His uptake and its metabolism is increased in SPE as a metabolic adaptation under nutritional starvation.…”

Quantification by real-time PCR of Trypanosoma cruzi DNA in samples of Triatoma infestans used in xenodiagnosis of chronic Chagas disease patients

“…Are demonstrated that XD is a useful tool to detect living T. cruzi in persons with CChD [ 46 ], therefore the positivity of PCR-XD and qPCR-XD suggests the presence of viable tripomastigotes naturally amplified by the biological vector. Nevertheless, diverse factors must be considered in the sensitivity of XD: number of boxes used, patient age, capacity of ingestion by the bugs [ 3 , 12 , 24 , 49 ], strong diuresis of triatomines with loss of initial inoculum after a large blood meal [ 14 , 32 ], complexity of the fecal metabolome of triatomines that suggests that it may affect triatomine competence for specific T. cruzi strains [ 1 ], bacterial microbiota in the triatomine gut [ 27 ]; influence of starvation in the development of T. cruzi in Tr. infestans [ 31 ], mortality during the incubation period and differential regulation of parasite populations that shows that some triatomine defense reactions discriminate not only between molecular signals specific for trypanosome infections but also between different strains of T. cruzi [ 25 ].…”

The Uptake and Metabolism of Amino Acids, and Their Unique Role in the Biology of Pathogenic Trypanosomatids

“…Epimastigotes in the early exponential growth phase ( in vitro ) are equipped with the complete set of glycolytic enzymes and, in fact, they obtain energy from glucose catabolism. However, it is not known if this is possible inside the insect midgut, since relevant quantities of free sugars in this environment have not been demonstrated so far [ 271 ]. However, the availability of amino acids has been well demonstrated [ 272 , 273 ] and the ability of epimastigotes to catabolize these metabolites is well understood, as previously described.…”