Induction of Autophagy interferes the tachyzoite to bradyzoite transformation ofToxoplasma gondii

Abstract

Autophagy process in Toxoplasma gondii plays a vital role in regulating parasite survival or death. Thus, once having an understanding of certain effects of autophagy on the transformation of tachyzoite to bradyzoite this will allow us to elucidate the function of autophagy during parasite development. Herein, we used three TgAtg proteins involved in Atg8 conjugation system, TgAtg3, TgAtg7 and TgAtg8 to evaluate the autophagy level in tachyzoite and bradyzoite of Toxoplasma in vitro based on Pru TgAtg7-HA transgenic strains. We showed that both TgAtg3 and TgAtg8 were expressed at a significantly lower level in bradyzoites than in tachyzoites. Importantly, the number of parasites containing fluorescence-labelled TgAtg8 puncta was significantly reduced in bradyzoites than in tachyzoites, suggesting that autophagy is downregulated in Toxoplasma bradyzoite in vitro. Moreover, after treatment with drugs, bradyzoite-specific gene BAG1 levels decreased significantly in rapamycin-treated bradyzoites and increased significantly in 3-MA-treated bradyzoites in comparison with control bradyzoites, indicating that Toxoplasma autophagy is involved in the transformation of tachyzoite to bradyzoite in vitro. Together, it is suggested that autophagy may serve as a potential strategy to regulate the transformation.

Xenophagy of invasive bacteria is differentially activated and modulated via a TLR-TRAF6-Beclin1 axis in echinoderms

“…Unlike bulk degradation of the packaged cargo in nonselective autophagy, xenophagy imparts selectivity to the degradation process by tagging and targeting cargoes into lysosomes (17). In mammalian species, the role of xenophagy in selectively eliminating disease-related pathogens, such as mycobacteria (19), HIV (46), and toxoplasma (49), has been well studied. However, the differential regulation mechanisms of xenophagy in response to different microbe challenges in a specific species, particularly an aquatic animal, remain largely unknown.…”

The heat shock protein 90 of Toxoplasma gondii is essential for invasion of host cells and tachyzoite growth

“…However, the factors and mechanisms governing the interconversion are poorly understood at the molecular level. Studies investigating the switch between the tachyzoite and bradyzoite have confirmed that the SAG1-related sequence (SRS) [27], zinc finger protein (ZFP1) [51], cyclic AMP-dependent protein kinase subunit 3 (PKAc3) [48], mitogen-activated protein kinase 1 (MAPK1) [7], and autophagy-related proteins (Atg) [29] are all involved in bradyzoite differentiation. In the present study, the transcriptional level of the Hsp90 gene was determined when T. gondii cells were under stress at 41 °C or pH 8.1.…”

Urolithin-A attenuates neurotoxoplasmosis and alters innate response towards predator odor

“…Notably, the upregulation of host autophagy pathway is reported to inhibit T. gondii growth ( Lee et al., 2020 ). Interestingly, the induction of T. gondii intrinsic autophagy activity has also been shown to interfere with tachyzoite to bradyzoite transformation ( Li et al., 2016 ). PE and UA are known to harbor autophagy-inducing activity ( Ryu et al., 2016 ; Tan et al., 2019 ).…”