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Arginine and polyamine availability modulates Toxoplasma growth independent of host arginase 2

ABSTRACT: Toxoplasma gondii is an obligate intracellular parasite that relies on host cell metabolism for essential nutrients it cannot synthesize independently, including arginine and its downstream products, polyamines. Hosts express two arginine-degrading enzymes: arginase 1, which is essential for ammonia detoxification in the liver, and arginase 2, a non-essential enzyme present in most tissues, including fibroblasts. While the function of arginase 1 in T. gondii infection has been examined, the potential role of arginase 2 in modulating nutrient availability for T. gondii is poorly understood. Here, we show that T. gondii growth, long-term replication, and stage conversion depend on environmental arginine availability, and this dependence is conserved across parasite strains and host cell types. Growth of T. gondii was enhanced by supplementation with polyamines, though the degree of enhancement varied by polyamine identity, an effect consistent across reagent vendors. Pharmacological inhibition of host arginase activity did not significantly alter parasite growth in either arginine-replete or arginine-restricted conditions. In arginase 2 knockout fibroblasts, parasite growth was indistinguishable between arginase 2 knockout and wild-type host cells under normal conditions, but significantly greater in knockout cells when environmental arginine was limited. This growth advantage was not accompanied by corresponding changes in parasite gene expression. Instead, host cells lacking arginase 2 showed transcriptional signatures of increased environmental arginine scavenging, which intensified during infection. Together, these findings suggest that T. gondii growth is governed by nutrient availability in its immediate environment over host arginase genotype.

ORGANISM(S): Mus musculus

PROVIDER: GSE346445 | GEO | 2026/09/11

REPOSITORIES: GEO

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Arginine and polyamine availability modulates Toxoplasma growth independent of host arginase 2

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