The Meaning of Death: Evolution and Ecology of Apoptosis in Protozoan Parasites

Abstract

The discovery that an apoptosis-like, programmed cell death (PCD) occurs in a broad range of protozoan parasites offers novel therapeutic tools to treat some of the most serious infectious diseases of humans, companion animals, wildlife, and livestock. Whilst apoptosis is an essential part of normal development, maintenance, and defence in multicellular organisms, its occurrence in unicellular parasites appears counter-intuitive and has proved highly controversial: according to the Darwinian notion of “survival of the fittest”, parasites are expected to evolve strategies to maximise their proliferation, not death. The prevailing, and untested, opinion in the literature is that parasites employ apoptosis to “altruistically” self-regulate the intensity of infection in the host/vector. However, evolutionary theory tells us that at most, this can only be part of the explanation, and other non-mutually exclusive hypotheses must also be tested. Here, we explain the evolutionary concepts that can explain apoptosis in unicellular parasites, highlight the key questions, and outline the approaches required to resolve the controversy over whether parasites “commit suicide”. We highlight the need for integration of proximate and functional approaches into an evolutionary framework to understand apoptosis in unicellular parasites. Understanding how, when, and why parasites employ apoptosis is central to targeting this process with interventions that are sustainable in the face of parasite evolution.

Altruism can evolve when relatedness is low: evidence from bacteria committing suicide upon phage infection

“…More generally, evolutionary conclusions based on proximate findings resulted in much controversy on whether mechanisms resulting in microbial cell death have indeed evolved for the purpose of committing suicide or whether they represent by-products of selection at other traits [34][35][36]. While this controversy can never distinctly be resolved for past events, it seems that in the Rex system, rexB may have originally been favoured because it protects E. coli from the killing mediated by addiction modules [37].…”

Just So Stories about the Evolution of Apoptosis

“…Active cell death processes are not unique to animals and have been described in plants [19], yeast [20], protozoa [21], and bacteria [22]. In some cases, attempts have been made to relate these events to apoptosis, sometimes implying an evolutionary relationship.…”

Statins and Voriconazole Induce Programmed Cell Death in Acanthamoeba castellanii

“…In these organisms, these apoptotic processes occur as a phenomenon that presumably benefits the rest of the population in some way. Kin selection may limit the spread of amoebic parasites through colonies or under conditions where limited nutrients may mean the survival of some cells at the expense of others (33,(40)(41)(42) or cell damage, such as that induced by chemotherapy (41). The fact that there is evidence that apoptotic processes exist in protozoan parasites has provided new strategies for the development of tools in the study of these diseases, comparing these processes to the one in humans (42).…”