Stress response pathways in protozoan parasites

Abstract

SummaryDiseases caused by protozoan parasites have a dramatic impact on world health. Emerging drug resistance and a general lack of experimental understanding has created a void in the medicine cabinet used to treat these widespread infections. A novel therapeutic idea that is receiving more attention is centred on targeting the microbe's response to the multitude of environmental stresses it encounters. Protozoan pathogens have complex life cycles, often having to transition from one host to another, or survive in a cyst form in the environment until a new host arrives. The need to respond to environmental cues and stress, and endure in less than optimal conditions, is paramount to their viability and successful progression through their life cycle. This review summarizes the research on parasitic stress responses for Apicomplexa, kinetoplastids and anaerobic protozoa, with an eye towards how these processes may be exploited therapeutically.

Phosphorylation of Translation Initiation Factor 2-Alpha in Leishmania donovani under Stress Is Necessary for Parasite Survival

“…In unicellular protozoan parasites, eIF2␣ phosphorylation under stress may induce the conversion of one form into another, which is distinguishable at morphological and biochemical levels (24). Cycling between cold-blooded insect vectors and warm-blooded mammalian hosts is typical for most parasitic protozoa, including Leishmania.…”

“…It is a classical serine-threonine kinase which undergoes autophosphorylation and is activated by the unfolded-protein response (UPR), a signal transduction pathway that coordinates cellular adaptation to microenvironmental stresses, including hypoxia, nutrient deprivation, and changes in the redox status (35,36). Protozoan parasites have eIF2␣ kinases that share the basic mechanistic features of their mammalian counterparts but have adapted different regulatory domain configurations, suggesting that the parasite eIF2␣ kinases may trigger translational control in response to different stress signals than those reported for mammals (24). Also, approaches to generate a PERK Ϫ/Ϫ mutant in the Leishmania diploid genome have so far been unsuccessful.…”

The Heat Shock Proteins of Trypanosoma cruzi

“…cruzi has to cope with several environmental changes, including shifts in temperature, low availability of nutrients, changes in osmolarity, and the presence of highly reactive oxidative species (ROS). The stress response in all these situations is similar to that of other protozoan parasites, and is varied and sophisticated (see reviews by Vonlaufen et al 2008 ;Urményi et al 2012 ). For example, T .…”

“…This interaction, in turn, affects innate and adaptive immunity and may infl uence survival of intracellular pathogens (reviewed by Srivastava 2002 ). HSPs and the heat stress response of protozoan parasites have been the subject of several recent reviews (Folgueira and Requena 2007 ;Vonlaufen et al 2008 ;Shonhai et al 2011 ). Digenetic parasites frequently are submitted to temperature changes during their life cycles, and HSPs are, as expected, part of their heat stress response.…”

Gene expression and molecular modeling of the HSP104 chaperone of Trypanosoma cruzi

“…The genome sequence of this parasite was recently completed, and proteomic analysis of the different stages of T. cruzi has been carried out, providing important evidence of stage-specific expression of numerous genes (Atwood et al, 2005). During its life cycle, T. cruzi, a digenetic parasite, undergoes several differentiation steps and a temperature shift when moving from the insect vector to the mammalian host, inducing heat shock proteins (HSPs) in the process (Rondinelli, 1994;Vonlaufen et al, 2008). HSPs are molecular chaperones and proteases that are induced under stress conditions to maintain protein homeostasis, and function in the intracellular environment (Hartl and Hayer-Hartl, 2002).…”