High-Throughput Repurposing Screen Reveals Compounds with Activity against Bradyzoites.

causes widespread chronic infections that are not cured by current treatments due to the inability to affect semidormant bradyzoite stages within tissue cysts. To identify compounds to eliminate chronic infection, we developed an HTS using a recently characterized strain of that undergoes efficient conversion to bradyzoites in vitro. Stage-specific expression of luciferase was used to selectively monitor the growth inhibition of bradyzoites by the Library of Pharmacological Active Compounds, consisting of 1280 drug-like compounds.

Phospho-relay feedback loops control egress vs. intracellular development in Toxoplasma gondii.

The intracellular parasite Toxoplasma gondii alternates between a motile invasive and a quiescent intracellular replicative form, yet how these transitions are regulated is unknown. A positive feedback loop involving protein kinase G (PKG) and calcium-dependent PKs (CDPKs) controls motility, invasion, and egress by Toxoplasma gondii, while PKA isoform c1 (PKAc1) counteracts this pathway. Shortly after invasion, PKAc1 is activated by cyclic AMP (cAMP) produced by adenylate cyclases, leading to the suppression of the PKG/CDPK pathway.

chitinase-like protein orchestrates cyst wall glycosylation to facilitate effector export and cyst turnover.

bradyzoites reside in tissue cysts that undergo cycles of expansion, rupture, and release to foster chronic infection. The glycosylated cyst wall acts as a protective barrier, although the processes responsible for formation, remodeling, and turnover are not understood. Herein, we identify a noncanonical chitinase-like enzyme TgCLP1 that localizes to micronemes and is targeted to the cyst wall after secretion.

Function of the alternative electron transport chain in the mitosome.

Unlabelled: possess a remanent mitochondrion called the mitosome, which lacks DNA, the tricarboxylic acid cycle, a conventional electron transport chain, and ATP synthesis. The mitosome retains ubiquinone and iron sulfur cluster biosynthesis pathways, both of which require protein import that relies on the membrane potential. It was previously proposed that the membrane potential is generated by electrons transferred through an alternative respiratory pathway coupled to a transhydrogenase (TH) that pumps hydrogens out of the mitosome.

MTBVAC induces superior antibody titers and IgG avidity compared to BCG vaccination in non-human primates.

The only currently licensed vaccine against tuberculosis (TB), Bacille Calmette Guérin (BCG), is insufficient to control the epidemic. MTBVAC is a live attenuated strain of Mycobacterium tuberculosis (M.tb) and is one the most advanced TB vaccine candidates in the pipeline.