Babesia gibsoni P-type sodium-transporting ATPase 4 (BgATP4) (BgATP4)

Babesia gibsoni P-type sodium-transporting ATPase 4 (BgATP4) is a vital transmembrane enzyme located on the plasma membrane of the protozoan parasite Babesia gibsoni, the causative agent of canine babesiosis (Murata et al., 2018, PMID: 30145158). Its primary biological function is the active extrusion of sodium ions from the parasite's cytoplasm to maintain a low intracellular sodium environment, which is crucial for osmotic balance and nutrient uptake (Spillman et al., 2013, PMID: 23510330). BgATP4 is a validated therapeutic target, as its inhibition by compounds such as spiroindolones (e.g., cipargamin) disrupts sodium homeostasis, leading to rapid influx of water, osmotic swelling, and subsequent lysis of the parasite. Because BgATP4 is structurally distinct from mammalian sodium-potassium ATPases, it offers a high degree of selectivity for antiprotozoal drug development. However, the clinical utility of targeting BgATP4 is challenged by the relative ease with which the parasite can develop resistance through specific point mutations in the ATP4 gene, such as those observed in laboratory-selected resistant strains (Murata et al., 2018, PMID: 30145158).

Other names

BgATP4P-type Na+-ATPaseSodium-extruding ATPaseATPase 4

Inhibition of the P-type Na+-ATPase leads to an increase in intracellular sodium concentration, resulting in osmotic stress, cellular swelling, and parasite death (Murata et al., 2018, PMID: 30145158).