Dissection of the in vitro developmental program of Hammondia hammondi reveals a link between stress sensitivity and life cycle flexibility in Toxoplasma gondii

Abstract

Most eukaryotic parasites are obligately heteroxenous, requiring sequential infection of different host species in order to survive. <i>Toxoplasma gondii</i> is a rare exception to this rule, having a uniquely facultative heteroxenous life cycle. To understand the origins of this phenomenon, we compared development and stress responses in <i>T. gondii</i> to those of its its obligately heteroxenous relative, <i>Hammondia hammondi</i> and have identified multiple <i>H. hammondi</i> growth states that are distinct from those in <i>T. gondii.</i> Of these, the most dramatic difference was that <i>H. hammondi</i> was refractory to stressors that robustly induce cyst formation in <i>T. gondii,</i> and this was reflected most dramatically in its unchanging transcriptome after stress exposure. We also found that <i>H. hammondi</i> could be propagated <i>in vitro</i> for up to 8 days post-excystation, and we exploited this to generate the first ever transgenic <i>H. hammondi</i> line. Overall our data show that <i>H. hammondi</i> zoites grow as stringently regulated, unique life stages that are distinct from <i>T. gondii</i> tachyzoites, and implicate stress sensitivity as a potential developmental innovation that increased the flexibility of the <i>T. gondii</i> life cycle.