Babesia gibsoni P-type ATPase 4 (BgATP4)

Babesia gibsoni P-type ATPase 4 (BgATP4) is a critical ion transporter located on the plasma membrane of the intraerythrocytic parasite Babesia gibsoni, which is a primary cause of canine babesiosis worldwide (elifesciences.org, 2024). It functions as a sodium-efflux pump, maintaining low cytosolic sodium levels essential for the parasite's survival and ionic homeostasis (elifesciences.org, 2024). This ionic gradient is vital for various physiological processes, including nutrient uptake and pH regulation (elifesciences.org, 2024). Disruption of this pump by inhibitors, such as the spiroindolone cipargamin (KAE609), leads to a rapid influx of sodium ions, causing osmotic stress, cellular swelling, and eventual parasite death (elifesciences.org, 2024). As B. gibsoni is often resistant to conventional treatments like imidocarb and atovaquone, BgATP4 has emerged as a promising therapeutic target for the development of novel antibabesial drugs (nih.gov, 2024). The target is highly conserved among apicomplexan parasites, making it a focal point for cross-species drug development efforts (elifesciences.org, 2024). Mutations in the BgATP4 gene, such as L921V and L921I, have been identified as mechanisms of resistance to cipargamin, highlighting the need for monitoring in clinical settings (elifesciences.org, 2024). Overall, BgATP4 represents a validated and potent target for the next generation of therapies aimed at eradicating Babesia infections in dogs (elifesciences.org, 2024).

Other names

BgATP4P-type Na+-ATPase 4Sodium-efflux ATPase 4Cation-transporting ATPase 4

Inhibition of the P-type ATPase 4 disrupts sodium efflux, leading to an increase in cytosolic sodium concentration, osmotic swelling, and parasite death.