Hydroxylamine and Carboxymethoxylamine Can Inhibit Growth through an Aspartate Aminotransferase-Independent Pathway.

is an obligate intracellular protozoan parasite and a successful parasitic pathogen in diverse organisms and host cell types. Hydroxylamine (HYD) and carboxymethoxylamine (CAR) have been reported as inhibitors of aspartate aminotransferases (AATs) and interfere with the proliferation in Therefore, AATs are suggested as drug targets against The genome encodes only one predicted AAT in both type I strain RH and type II strain PLK. However, the effects of HYD and CAR, as well as their relationship with AAT, on remain unclear. In this study, we found that HYD and CAR impaired the lytic cycle of , including the inhibition of invasion or reinvasion, intracellular replication, and egress. Importantly, HYD and CAR could control acute toxoplasmosis Further studies showed that HYD and CAR could inhibit the transamination activity of rAAT However, our results confirmed that deficiency of AAT in both RH and PLK did not reduce the virulence in mice, although the growth ability of the parasites was affected HYD and CAR could still inhibit the growth of AAT-deficient parasites. These findings indicated that HYD and CAR inhibition of growth and control of toxoplasmosis can occur in an AAT-independent pathway. Overall, further studies focusing on the elucidation of the mechanism of inhibition are warranted. Our study hints at new substrates of HYD and CAR as potential drug targets to inhibit growth.