Role of Toxoplasma gondii Chloroquine Resistance Transporter in Bradyzoite Viability and Digestive Vacuole Maintenance

MBio
Geetha KannanVern B. Carruthers

Abstract

Toxoplasma gondii is a ubiquitous pathogen that can cause encephalitis, congenital defects, and ocular disease. T. gondii has also been implicated as a risk factor for mental illness in humans. The parasite persists in the brain as slow-growing bradyzoites contained within intracellular cysts. No treatments exist to eliminate this form of parasite. Although proteolytic degradation within the parasite lysosome-like vacuolar compartment (VAC) is critical for bradyzoite viability, whether other aspects of the VAC are important for parasite persistence remains unknown. An ortholog of Plasmodium falciparum chloroquine resistance transporter (CRT), TgCRT, has previously been identified in T. gondii To interrogate the function of TgCRT in chronic-stage bradyzoites and its role in persistence, we knocked out TgCRT in a cystogenic strain and assessed VAC size, VAC digestion of host-derived proteins and parasite autophagosomes, and the viability of in vitro and in vivo bradyzoites. We found that whereas parasites deficient in TgCRT exhibit normal digestion within the VAC, they display a markedly distended VAC and their viability is compromised both in vitro and in vivo Interestingly, impairing VAC proteolysis in TgCRT-deficient bradyzoit...Continue Reading

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Citations

Oct 2, 2019·Frontiers in Cellular and Infection Microbiology·Tatiana Paredes-SantosJeroen P Saeij
Jan 29, 2021·MSphere·Geetha KannanVern B Carruthers

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Methods Mentioned

BETA
electron microscopy
PCR
PCRs
flow cytometry
fluorescence imaging
enzyme-linked immunosorbent assay

Software Mentioned

ROUT
FACSDiVa
ImageJ
BD

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