Equal Inheritance: Genome Management for Proliferating Parasites

Abstract

Of the 1,400 or so known human pathogen species, those belonging to the Apicomplexa phylum represent a special challenge to researchers. These singlecelled protists cause some of the world’s most prevalent parasitic diseases, including malaria (Plasmodium falciparum) and toxoplasmosis (Toxoplasma gondii). They are challenging to treat for two reasons. First, the parasites are eukaryotic and thus more similar to human cells than bacterial pathogens, making it difficult to find treatments that kill the parasite without harming human host cells. Second, the parasite cells reside within human host cells for much of their life cycle, evading detection by the host’s immune system. Apicomplexan parasites are named for a unique structure, the apical complex, which is present on the apical end of the parasite cell and enables the parasite to penetrate a host cell within seconds of contact. Once within a host cell, the parasite replicates and divides. T. gondii exhibit the simplest pattern of cell division, generally assembling two daughter cells within a mother cell, which then splits to produce the two daughter cells. Other species, like P. falciparum, may undergo multiple consecutive rounds of nuclear division, resulting in many copies of the parasite’s DNA within one engorged cell, before splintering into as many as tens or thousands of daughter cells. The number of daughter cells can depend on the stage of the parasite and on which type of cell it has invaded. A P. falciparum parasite produces 10 to 20 daughter cells within a red blood cell and thousands of daughter cells within a liver cell. This peculiar form of replication leads to interesting questions. With potentially tens or thousands of nuclei waiting in the replicating cell, how does the parasite know how many daughter cells it will need to accommodate the nuclei? And how does it distribute the nuclei to the daughter cells? In this issue of PLOS Biology, Maria Francia, Boris Striepen, and colleagues describe a fiber-like structure in T. gondii cells that appears to match each newly formed nucleus to a daughter cell, ensuring that each new parasite receives exactly one nucleus. The team found that two proteins called TgSFA2 and TgSFA3 together formed two short fibers in the dividing parasite cell. Further microscopic work suggested these fibers may be important for cell division, because the SFA fibers appeared to form near the centrosome. In animal cells, centrosomes serve as organizing centers for the spindle, a set of microtubule protein fibers that reach into the mass of replicated chromosomes and pull the chromosomes apart into two equal sets during cell division. In fact, the team observed that the SFA fibers formed only after the centrosome split in two, a key event occurring at the start of cell division. The fibers eventually grew longer, extending away from the centrosomes and reaching into the developing daughter cells, ultimately terminating on their apical end. Further experiments showed that the SFA fiber did not merely link the centrosome and developing daughter cells, but was required for the proper formation of the daughter cells. The researchers con-