A Patatin-Like Protein Protects Toxoplasma gondii from Degradation in a Nitric Oxide-Dependent Manner

Department of Medical Microbiology and Immunology, University of Wisconsin—Madison, Madison, Wisconsin, USA.
Infection and immunity (Impact Factor: 3.73). 01/2012; 80(1):55-61. DOI: 10.1128/IAI.05543-11
Source: PubMed


Toxoplasma gondii is an obligate intracellular parasite that uses immune cells to disseminate throughout its host. T. gondii can persist and even slowly replicate in activated host macrophages by reducing the antimicrobial effects of molecules such
as nitric oxide (NO). A T. gondii patatin-like protein called TgPL1 was previously shown to be important for survival in activated macrophages. Here we show
that a T. gondii mutant with a deletion of the TgPL1 gene (ΔTgPL1) is degraded in activated macrophages. This degradation phenotype is abolished by the removal of NO by the use
of an inducible NO synthase (iNOS) inhibitor or iNOS-deficient macrophages. The exogenous addition of NO to macrophages results
in reduced parasite growth but not the degradation of ΔTgPL1 parasites. These results suggest that NO is necessary but not
sufficient for the degradation of ΔTgPL1 parasites in activated macrophages. While some patatin-like proteins have phospholipase
A2 (PLA2) activity, recombinant TgPL1 purified from Escherichia coli does not have phospholipase activity. This result was not surprising, as TgPL1 contains a G-to-S change at the predicted
catalytic serine residue. An epitope-tagged version of TgPL1 partially colocalized with a dense granule protein in the parasitophorous
vacuole space. These results may suggest that TgPL1 moves to the parasitophorous vacuole to protect parasites from nitric
oxide by an undetermined mechanism.

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