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The Trypanosoma cruzi parasite is able to invade almost any cell type, circulate freely in the blood or extracellular matrix, pass through the digestive tract of its insect vector and survive after being eliminated in the feces. It is also capable of infecting many mammals, including humans. This versatility of invasion and infection gives this parasite a virtually unique characteristic when compared to other pathogens. To cope with these characteristics requires a great adaptive capacity, and a fine regulation of gene expression, to allow adaptation to such different environments. This seems to go in the opposite direction of what is usually known about these parasitic protozoa, that they do not present the classical eukaryotic gene regulation mechanisms, and that their tendency is to transcribe most of the open reading frames, proceeding later to a posttranscriptional regulation. The surface envelope of T. cruzi, which is in a certain way its "letter of introduction" to the different cell types and/or immune systems they face, may constitute one of the explanations for the broad spectrum of infective capacity of these parasites. This surface is mainly constituted by three protein families encoded by hundreds of genes: mucin-like proteins (MUC), transialidases (TS) and mucin-associated proteins (MASP). They are GPI-anchored, with MUC and TS having been extensively studied, while MASP were discovered more recently, when the genome sequence of T. cruzi was first determined. An additional feature is that their genes are in the same regions of the genome. Thus, the T. cruzi genome consists of a core compartment (CC) with a high degree of synteny with the rest of the trypanosomatids (Leishmania spp., African trypanosomes), and a disruptive compartment (DC) where synteny with these species is lost. There are disruptive chromosomes (DC>90%), core chromosomes (CC>90%) and mixed chromosomes. Analyzing the steady state levels of mRNA we see that CC presents high and medium levels of expression -independently of the stage- and DC presents low levels of expression, also in all stages. On the other hand, the analysis of differentially expressed genes shows that in the CC they are distributed similarly in the different stages, while the CR shows highly significant differential expression in the trypomastigote stage, indicating that it is a genome specialized in the host-pathogen interaction. These different expression characteristics between compartments are due to epigenetic mechanisms and chromatin organization: chromosomal interactions, chromatin condensation, nucleosome positioning and methylation patterns, which seem to be determinant in the properties of each compartment. [ABSTRACT FROM AUTHOR]

Trypanosoma cruzi, the causative agent of Chagas disease, has the peculiarity, when compared with other intracellular parasites, that it is able to invade almost any type of cell. This property makes Chagas a complex parasitic disease in terms of prophylaxis and therapeutics. The identification of key host cellular factors that play a role in the T. cruzi invasion is important for the understanding of disease pathogenesis. In Chagas disease, most of the focus is on the response of macrophages and cardiomyocytes, since they are responsible for host defenses and cardiac lesions, respectively. In the present work, we studied the early response to infection of T. cruzi in human epithelial cells, which constitute the first barrier for establishment of infection. These studies identified up to 1700 significantly altered genes regulated by the immediate infection. The global analysis indicates that cells are literally reprogrammed by T. cruzi, which affects cellular stress responses (neutrophil chemotaxis, DNA damage response), a great number of transcription factors (including the majority of NFκB familymembers), and hostmetabolism(cholesterol, fatty acids, and phospholipids). These results raise the possibility that early host cell reprogramming is exploited by the parasite to establish the initial infection and posterior systemic dissemination. [ABSTRACT FROM AUTHOR]

Protozoan parasites are responsible of important healthy problems, among others malaria, leishmaniasis and trypanosomiasis. The present work reports the characterization of the first mammalian ATP-binding cassette transporter, subfamily A (ABCA)-like inTrypanosoma cruzi.TcABC1is a single copy gene differentially expressed along the life cycle of the parasite, being absent in its infective form. TcABC1 localizes to the plasma membrane, flagellar pocket and intracellular vesicles. Functional studies of TcABC1 in transfected parasites suggest that the protein is implicated in intracellular trafficking, as determined by the analysis of endocytosis and exocytosis events. The accumulation of the endocytic markers FM4-64 and NBD-SM is increased in transfected parasites. Similarly, ectophosphatase and ectoATPase activities are increased in TcABC1 overproducers. Indeed, transmission electronic microscopy analysis showed a higher number of intracellular vesicles in TcABC1 transfectants. Taken together, these results suggest that the protein is involved in the endocytic and exocytic pathways ofT. cruzi. [ABSTRACT FROM AUTHOR]