The Influence of Environmental Cues on the Development of Trypanosoma cruzi in Triatominae Vector

Melo, Raíssa de Fátima Pimentel; Guarneri, Alessandra A.; Silber, Ariel Mariano

doi:10.3389/fcimb.2020.00027

Cited by 34 publications

(33 citation statements)

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“…After being released from infected cells, trypomastigotes can spread the infection by infecting new cells, or they can be ingested by a triatomine bug during its blood meal. Once inside the invertebrate host, the ingested trypomastigotes differentiate into epimastigotes, which initiate their proliferation and colonization of the insect digestive tract [ 3 ]. Once the epimastigotes reach the final portion of the digestive tube, they initiate differentiation into non-proliferative, infective metacyclic trypomastigotes.…”

Section: Introductionmentioning

confidence: 99%

“…The diversity of environments through which T . cruzi passes during its life cycle (i.e., the digestive tube of the insect vector, the bloodstream and the mammalian cells cytoplasm) subjects it to different levels of nutrient availability [ 3 , 7 ]. Therefore, this organism evolved a robust, flexible and efficient metabolism [ 4 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Fatty acid oxidation participates in resistance to nutrient-depleted environments in the insect stages of Trypanosoma cruzi

et al. 2021

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Trypanosoma cruzi, the parasite causing Chagas disease, is a digenetic flagellated protist that infects mammals (including humans) and reduviid insect vectors. Therefore, T. cruzi must colonize different niches in order to complete its life cycle in both hosts. This fact determines the need of adaptations to face challenging environmental cues. The primary environmental challenge, particularly in the insect stages, is poor nutrient availability. In this regard, it is well known that T. cruzi has a flexible metabolism able to rapidly switch from carbohydrates (mainly glucose) to amino acids (mostly proline) consumption. Also established has been the capability of T. cruzi to use glucose and amino acids to support the differentiation process occurring in the insect, from replicative non-infective epimastigotes to non-replicative infective metacyclic trypomastigotes. However, little is known about the possibilities of using externally available and internally stored fatty acids as resources to survive in nutrient-poor environments, and to sustain metacyclogenesis. In this study, we revisit the metabolic fate of fatty acid breakdown in T. cruzi. Herein, we show that during parasite proliferation, the glucose concentration in the medium can regulate the fatty acid metabolism. At the stationary phase, the parasites fully oxidize fatty acids. [U-14C]-palmitate can be taken up from the medium, leading to CO2 production. Additionally, we show that electrons are fed directly to oxidative phosphorylation, and acetyl-CoA is supplied to the tricarboxylic acid (TCA) cycle, which can be used to feed anabolic pathways such as the de novo biosynthesis of fatty acids. Finally, we show as well that the inhibition of fatty acids mobilization into the mitochondrion diminishes the survival to severe starvation, and impairs metacyclogenesis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fatty acid oxidation participates in resistance to nutrient-depleted environments in the insect stages of Trypanosoma cruzi

et al. 2021

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“…The diversity of environments through which T. cruzi passes during its life cycle (i.e., the digestive tube of the insect vector, the bloodstream and the mammalian cells cytoplasm) subjects it to different levels of nutrient availability [3,7]. Therefore, this organism evolved a robust, flexible and efficient metabolism [5,8].…”

Section: Introductionmentioning

confidence: 99%

Fatty acid oxidation participates of the survival to starvation, cell cycle progression and differentiation in the insect stages ofTrypanosoma cruzi

Souza

Damasceno

Marsiccobetre

et al. 2021

Preprint

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During its complex life cycle, Trypanosoma cruzi colonizes different niches in its insect and mammalian hosts. This characteristic determined the types of parasites that adapted to face challenging environmental cues. The primary environmental challenge, particularly in the insect stages, is poor nutrient availability. These T. cruzi stages could be exposed to fatty acids originating from the degradation of the perimicrovillar membrane. In this study, we revisit the metabolic fate of fatty acid breakdown in T. cruzi. Herein, we show that during parasite proliferation, the glucose concentration in the medium can regulate the fatty acid metabolism. At the stationary phase, the parasites fully oxidize fatty acids. [U-14C]-palmitate can be taken up from the medium, leading to CO2 production via beta-oxidation. Lastly, we also show that fatty acids are degraded through beta-oxidation. Additionally, through beta-oxidation, electrons are fed directly to oxidative phosphorylation, and acetyl-CoA is supplied to the tricarboxylic acid cycle, which can be used to feed other anabolic pathways such as the de novo biosynthesis of fatty acids.Author SummaryTrypanosoma cruzi is a protist parasite with a life cycle involving two types of hosts, a vertebrate one (which includes humans, causing Chagas disease) and an invertebrate one (kissing bugs, which vectorize the infection among mammals). In both hosts, the parasite faces environmental challenges such as sudden changes in the metabolic composition of the medium in which they develop, severe starvation, osmotic stress and redox imbalance, among others. Because kissing bugs feed infrequently in nature, an intriguing aspect of T. cruzi biology (it exclusively inhabits the digestive tube of these insects) is how they subsist during long periods of starvation. In this work, we show that this parasite performs a metabolic switch from glucose consumption to lipid oxidation, and it is able to consume lipids and the lipid-derived fatty acids from both internal origins as well as externally supplied compounds. When fatty acid oxidation is chemically inhibited by etomoxir, a very well-known drug that inhibits the translocation of fatty acids into the mitochondria, the proliferative insect stage of the parasites has dramatically diminished survival under severe metabolic stress and its differentiation into its infective forms is impaired. Our findings place fatty acids in the centre of the scene regarding their extraordinary resistance to nutrient-depleted environments.

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“…Chagas disease (ChD) is caused by the protozoan parasite Trypanosoma cruzi, which infects humans and more than 100 species of domestic and sylvatic mammals and can be transmitted by over 150 species of hemiptera insects of the subfamily Triatominae (Reduviidae) [1][2][3][4]. ChD has become one of the biggest public-health problems in Latin America due to its incapacitating effects and mortality rates [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Echocardiographic Findings in Canine Model of Chagas Disease Immunized with DNA Trypanosoma cruzi Genes

Rodríguez-Morales

Roldán

Vargas-Barrón

et al. 2020

Animals

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Simple Summary: Chagas disease (ChD) has become one of the biggest public-health problems in Latin America due to its incapacitating effects and mortality rates. Therefore, it is important to detect cardiac involvement as early as possible in order to estimate the risk and prognosis before the patient becomes symptomatic. Development of anti-Trypanosoma cruzi vaccines could significantly contribute to the control of ChD. The aim of this study was to examine the usefulness of echocardiography in determining the prophylactic effect of the DNA vaccines on heart damage using T. cruzi genes cloned into an expression vector, which was intramuscularly injected to beagle dogs. Structural and functional changes in the chagasic heart were monitored easily by echocardiography, and it was determined that plasmid DNA vaccination with T. cruzi genes induced moderate protection in immunized dogs avoiding enlargement of cardiac chambers, poor contractibility, and heart failure, especially with pBCSP plasmid (the construct with TcSP gene of T. cruzi, encoding trans-sialidase protein), as was reported previously.Abstract: Chagas disease (ChD) is considered an emerging disease in the USA and Europe. Trypanosoma cruzi genes encoding a trans-sialidase protein and an amastigote-specific glycoprotein were tested as vaccines in canine model. The aim for this study was determining the prophylactic effect of these genes in experimentally infected dogs by echocardiography evaluation to compare with our findings obtained by other techniques published previously. Low fractional-shortening values of non-vaccinated dogs suggested an impairment in general cardiac function. Low left ventricular ejection fraction values found in infected dogs suggested myocardial injury regardless of whether they were vaccinated. Low left ventricular diastolic/systolic diameters suggested that progressive heart damage or heart dilation could be prevented by DNA vaccination. Systolic peak time was higher in non-vaccinated groups, increasing vulnerability to malignant arrhythmias and sudden death. High left ventricular volume suggested a decrease in wall thickness that might lead to increased size of the heart cavity, except in the pBCSP plasmid-vaccinated dogs. There was an echocardiographic evidence of left ventricular dilation and reduction in systolic function in experimental chagasic dogs. Echocardiography allowed a more complete follow-up of the pathological process in the living patient than with other techniques like electrocardiography, anatomopathology, and histopathology, being the method of choice for characterizing the clinical stages of ChD.

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The Influence of Environmental Cues on the Development of Trypanosoma cruzi in Triatominae Vector

Cited by 34 publications

References 64 publications

Fatty acid oxidation participates in resistance to nutrient-depleted environments in the insect stages of Trypanosoma cruzi

Fatty acid oxidation participates in resistance to nutrient-depleted environments in the insect stages of Trypanosoma cruzi

Fatty acid oxidation participates of the survival to starvation, cell cycle progression and differentiation in the insect stages ofTrypanosoma cruzi

Echocardiographic Findings in Canine Model of Chagas Disease Immunized with DNA Trypanosoma cruzi Genes

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