Biochemistry of Chagas disease

Biochemistry of the parasite 

Trypanosomes contain a variety of enzymes such as proteases, gelatinases, and collagenases that are capable of degrading native type I collagen, heat-denatured type I collagen (gelatin), and native type IV collagen (42, 78, 98). Proteolytic activities against laminin and fibronectin were also detected. These enzymes are most likely responsible for the degradation of the ECM and the subsequent tissues to aid in the parasite's invasion into the bloodstream.

The degradation of the collagen matrix, evident in acute murine Chagas' disease, may result in chronic pathologic changes such as apical thinning (77, 182). Finally, supernatants obtained from cultures of infected fibroblasts, vascular smooth muscle cells, and myocardial cells were found to stimulate fibroblast DNA and protein synthesis as well as proliferation, whereas supernatants from uninfected cells did not. This suggests that there is a mechanism by which fibrosis may occur in chronic chagasic cardiomyopathy (284).

The relationship between this enzyme and T. cruzi transsialidase has recently been investigated (230).It was found out that T. cruzi neuraminidase is inhibited by anti-neuraminidase antibodies and high-density lipoprotein, which is associated with enhanced infectivity of cells in vitro (202, 203). The significance of these observations in the pathogenesis of Chagas' disease is unclear. However, it is noteworthy that mice with higher levels of high-density lipoprotein are more susceptible to T. cruzi infection (202). The relationship between the synthesis of these parasite enzymes and the pathogenesis of the disease remains to be elucidated.

Note that most of the above results and conclusions are obtained directly from the research paper, and none of which are results obtained on my own. Please click on the link at the bottom of this update for the full paper.

Biochemistry of invasion

Trypomastigotes are refractory to complement-mediated lysis, whereas epimastigotes activate the alternate complement pathway. The mechanism of the resistance of trypomastigotes to complement is unclear, and several different mechanisms have been proposed (104, 114, 115, 235). Amastigotes activate complement but are not lysed. Trypomastigotes bind small amounts of C3 but can also infect cells that do not have C3 fragment receptors. Other host cell surface molecules may be important in the process of entry into the cell. In this regard, it has been suggested that fibronectin increases the internalization of trypomastigotes in both phagocytic and nonphagocytic cells (53) and may act as a bridge to facilitate the attachment of the parasite to the target host cell (104).The parasite undergoes a complex process involving a variety of different factors to gain host cell entry and (216). Schenkman et al. (229) shows that trypomastigotes enter cells in a polarized manner preferably along the basolateral membrane, where there is a concentrated amount of fibronectin and host cell receptors. Thus the invasion is an active process associated with factors such ashost cell protein synthesis and parasite energy(232). Parasite phospholipase A2 has also been implicated in this process (49). A T. cruzi trans-sialidase has been shown to have facilitated the generation of a trypomastigote-specific epitope, Ssp-3,which is required for invasion (231). The entry of trypomastigotes into the host cells has not been reported to be associated with a respiratory burst, suggesting that non-oxidative intracellular mechanisms may be important in limiting intracellular infection (151). Parasites may be killed by cytocidal mechanisms such as production of hydrogen peroxide within the parasitophorous vacuole. This process may be associated with lysosomal fusion (247, 256).

Note that most of the above results and conclusions are obtained directly from the research paper, and none of which are results obtained on my own. Please click on the link at the bottom of this update for the full paper.

Biochemistry of Differentiation In the complex

Three morphogenetic forms of the parasite can be recognized in the life cycle of T. cruzi

From the life cycle, these parasites multiply as epimastigotes in the midgut of the insect vector. After transformation into metacyclic trypomastigotes, the organisms are deposited with the faeces of the vector and infect mammalian cells in mucosal surfaces, conjunctiva, or breaks in the skin. Once it has successfully invaded the host cells, the parasites transform into amastigotes and, after several cycles of multiplication, revert back into bloodstream amastigotes, which are morphologically similar to the trypomastigotes present in insect faeces. The host cell then ruptures, releasing these parasites into the adjacent tissues and blood circulation. The cycle is completed when the circulating trypomastigotes are ingested in a blood meal taken by another insect vector and transforms in to epimastigotes in its midgut.

Ref:
http://cmr.asm.org/content/5/4/400.full.pdf