Stress sensitivity in Toxoplasma gondii is linked to its uniquely flexible life cycle

Authors: SOKOL, SARA - University Of Pittsburgh; PRIMACK, ABBY - University Of Pittsburgh; NAIR, SETHU - University Of Pittsburgh; WONG, ZHEE - University Of Pittsburgh; TEMBOO, MAIWASE - University Of Pittsburgh; Dubey, Jitender; VERMA, SHIV - Non ARS Employee; BOYLE, JON - University Of Pittsburgh

Submitted to: eLife
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/18/2018
Publication Date: 5/22/2018
Citation: Sokol, S., Primack, A., Nair, S., Wong, Z., Temboo, M., Dubey, J.P., Verma, S., Boyle, J. 2018. Stress sensitivity in Toxoplasma gondii is linked to its uniquely flexible life cycle. eLife. e36491. https://doi.org/10.7554/eLife.36491
DOI: https://doi.org/10.7554/eLife.36491

Interpretive Summary: Toxoplasma gondii is an intracellular parasite that infects up to one-quarter of humans worldwide. Although it can infect virtually any warmblooded animal, its definitive host is the cat where the sexual cycle occurs in enterocytes of the small intestine, producing microscopic, durable oocysts that are shed in feces and can remain infectious for extended periods of time in the environment. Hammondia hammondi is the nearest extant relative of T. gondii. Despite sharing >99% of their genes in near perfect synteny ) and the same definitive host, H. hammondi is only known to naturally infect rodents, goats, and roe deer. Unlike T. gondii, H. hammondi does not cause illness in any host. In the present paper the authors define the life cycle of H. hammondi in detail. The authors report first recombinant H. hammondi , opening up the door to future molecular and genetic studies in this poorly understood parasite species These results will be of interest to biologists, microbiologists, and parasitologists.

Technical Abstract: Hammondia hammondi is the nearest relative of Toxoplasma gondii, but unlike T. gondii is obligately heteroxenous. We have compared H. hammondi and T. gondii development in vitro and identified multiple H. hammondi-specific growth states. Despite replicating slower than T. gondii, H. hammondi was resistant to pH-induced tissue cyst formation early after excystation. However, in the absence of stress H. hammondi spontaneously converted to a terminally differentiated tissue cyst stage while T. gondii did not. Cultured H. hammondi could infect new host cells for up to 8 days following excystation, and this period was exploited to generate stably transgenic H. hammondi. Coupled with RNAseq analyses, our data clearly show that H. hammondi zoites grow as stringently regulated life stages that are fundamentally distinct from T. gondii tachyzoites and bradyzoites.