Leishmania plasma membrane phospholipids and 24-alkylated sterols

The plasma membrane of Leishmania parasites is a complex assembly of phospholipids and unique 24-alkylated sterols, such as ergosterol and 5-dehydroepisterol, which are distinct from the cholesterol found in mammalian membranes (Goad et al., 1984). These lipids are essential for maintaining membrane integrity, fluidity, and the function of membrane-bound proteins required for the parasite's survival and infectivity (Roberts et al., 2003). Because of these biochemical differences, the membrane lipids serve as critical targets for anti-leishmanial drugs (Croft et al., 2006). Amphotericin B, a polyene macrolide, binds with high affinity to 24-alkylated sterols, leading to the formation of aqueous pores that cause the leakage of essential ions and subsequent cell death (Baginski and Czub, 2009). Miltefosine, an alkylphosphocholine, targets the phospholipid metabolism and disrupts intracellular signaling pathways, further compromising the parasite's membrane stability (Dorlo et al., 2012). The specificity of these interactions allows for the selective targeting of the parasite over the host, although the development of resistance and the inherent toxicity of some agents remain significant clinical challenges.

Other names

Leishmania membrane lipidsLeishmania ergosterol-like sterolsLeishmania cell membraneParasite membrane sterols and phospholipids

Polyene antibiotics like Amphotericin B bind directly to 24-alkylated sterols (ergosterol-like) to form trans-membrane pores, leading to ion leakage and osmotic lysis; alkylphosphocholines like Miltefosine interfere with phospholipid metabolism and cell signaling pathways.