Plasticity and Redundancy in Proteins Important for Toxoplasma Invasion

Phenotypic plasticity encompasses the versatile abilities of an organism to modify its phenotype according to changes in the environment. Such adaptations, in response to a decrease of fitness, are commonly exploited by microorganisms and plants that cannot easily escape their environment and, hence, are at risk of extinction. Functional redundancy and plasticity is therefore anticipated for obligate intracellular parasites, including members of the phylum Apicomplexa, to ensure successful host cell invasion—a critical step for their survival. The phylum Apicomplexa includes many medically and veterinary-relevant parasites, most notably the human pathogens Plasmodium and Toxoplasma gondii, responsible for malaria and toxoplasmosis, respectively. These parasites are the most studied of the phylum, not only because of their prevalence but also because of their accessibility to genetic manipulation [1,2], which has allowed the investigation of several aspects of their lytic cycle, particularly their mechanisms of entry into the target cell. Invasion by most Apicomplexa is a multistep process consisting of recognition, attachment, and active penetration into host cells, which has been dissected in depth in Toxoplasma tachyzoites [3]. Parasite propulsion into the host cell is powered by a myosin motor complex termed the glideosome. During motility and invasion, T. gondiimyosin A (TgMyoA) presumably translocates adhesins at the moving junction (MJ) from the apical to the posterior pole of the parasite [4]. The MJ forms a constriction around the parasite at the point of entry into the host cell that appears as a ring structure. Apical membrane antigen 1 (AMA1) in association with a complex of rhoptry neck proteins (RONs) that are anchored into the host cortical cytoskeleton [5] are the currently known components of this MJ. Insults imposed upon the parasite by experimental genome editing strategies, such as ablation of TgMyoA and TgAMA1 genes, significantly compromised the fitness of the parasites and have now been demonstrated to elicit phenotypic plasticity. Such plasticity has uncovered informative redundancy and adaptation mechanisms. Hereafter, we compare and contrast the methodologies available to investigate the function of crucial genes in T. gondii and discuss how some experimental approaches contribute to or even favor the emergence of alternative mechanisms to ensure completion of the vital step of host cell invasion.