Trypanosoma cruzi, the protozoan responsible for Chagas disease, has a complex life cycle comprehending two distinct hosts and a series of morphological and functional transformations. Hemoglobin degradation inside the insect vector releases high amounts of heme, and this molecule is known to exert a number of physiological functions. Moreover, the absence of its complete biosynthetic pathway in T. cruzi indicates heme as an essential molecule for this trypanosomatid survival. Within the hosts, T. cruzi has to cope with sudden environmental changes especially in the redox status and heme is able to increase the basal production of reactive oxygen species (ROS) which can be also produced as byproducts of the parasite aerobic metabolism. In this regard, ROS sensing is likely to be an important mechanism for the adaptation and interaction of these organisms with their hosts. In this paper we discuss the main features of heme and ROS susceptibility in T. cruzi biology. 1. Trypanosoma cruzi and Its Biological Cycle Trypanosoma cruzi comprises a complex group of parasite populations circulating among humans, vectors, reservoirs, and wild and domestic animals [1]. This parasite is the causative agent of Chagas disease or American trypanosomiasis [2] and is transmitted through triatomine vectors, which are blood-sucking insects, when they feed on the vertebrate host. After an insect feeds on the blood of an infected vertebrate, the development cycle of the parasite begins in the intestinal tract of triatomines. In the anterior midgut, most blood trypomastigotes transform into epimastigotes a few hours after ingestion. Some epimastigotes multiply by longitudinal binary fission, and in the insect rectum, a new differentiation occurs (metacyclogenesis process) in which epimastigotes are transformed into metacyclic trypomastigotes. These metacyclic trypomastigotes (highly infectious) are shed in feces and reach the bloodstream of a new vertebrate host after this host scratches an insect bite. The organisms penetrate the mucosa where there are many macrophages; after intense multiplication in the host cell in the form of amastigotes, they transform into trypomastigotes again, returning to the vertebrate circulation and completing the cycle [3]. These series of morphological and biochemical transformations in the life cycle may occur in response to external stimuli [4]. Recently, reactive oxygen species (ROS) and heme have been hypothesized to be important signaling molecules. In this way, protozoan parasites, which are specifically located in places where these
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