Sexual Development in Non-Human Parasitic Apicomplexa: Just Biology or Targets for Control?

SIMPLE SUMMARY: Cellular reproduction is a key part of the apicomplexan life cycle, and both mitotic (asexual) and meiotic (sexual) cell divisions produce new individual cells. Sexual reproduction in most eukaryotic taxa indicates that it has had considerable success during evolution, and it must confer profound benefits, considering its significant costs. The phylum Apicomplexa consists of almost exclusively parasitic single-celled eukaryotic organisms that can affect a wide host range of animals from invertebrates to mammals. Their development is characterized by complex steps in which asexual and sexual replication alternate and the fertilization of a macrogamete by a microgamete results in the formation of a zygote that undergoes meiosis, thus forming a new generation of asexual stages. In apicomplexans, sex is assumed to be induced by the (stressful) condition of having to leave the host, and either gametes or zygotes (or stages arising from it) are transmitted to a new host. Therefore, sex and meiosis are linked to parasite transmission, and consequently dissemination, which are key to the parasitic lifestyle. We hypothesize that improved knowledge of the sexual biology of the Apicomplexa will be essential to design and implement effective transmission-blocking strategies for the control of the major parasites of this group. ABSTRACT: The phylum Apicomplexa is a major group of protozoan parasites including gregarines, coccidia, haemogregarines, haemosporidia and piroplasms, with more than 6000 named species. Three of these subgroups, the coccidia, hemosporidia, and piroplasms, contain parasites that cause important diseases of humans and animals worldwide. All of them have complex life cycles involving a switch between asexual and sexual reproduction, which is key to their development. Fertilization (i.e., fusion of female and male cells) results in the formation of a zygote that undergoes meiosis, forming a new generation of asexual stages. In eukaryotes, sexual reproduction is the predominant mode of recombination and segregation of DNA. Sex is well documented in many protist groups, and together with meiosis, is frequently linked with transmission to new hosts. Apicomplexan sexual stages constitute a bottleneck in the life cycle of these parasites, as they are obligatory for the development of new transmissible stages. Consequently, the sexual stages represent attractive targets for vaccination. Detailed understanding of apicomplexan sexual biology will pave the way for the design and implementation of effective transmission-blocking strategies for parasite control. This article reviews the current knowledge on the sexual development of Apicomplexa and the progress in transmission-blocking vaccines for their control, their advantages and limitations and outstanding questions for the future.