Leishmania

Leishmania is an obligate intracellular protozoan parasite transmitted by sand flies, and mammalian infection centers on macrophages as both host cells and immune effector cells^[1]. Mechanistically, the parasite regulates phagosome maturation to support intracellular growth and avoid destruction after uptake into macrophages^[1]. Lipophosphoglycan (LPG) is a surface glycoconjugate virulence factor that supports metacyclic establishment in host cells but declines during amastigote development^[2]. Compared with related glycoconjugates, LPG showed a distinct virulence role in Leishmania major, because lpg mutants were attenuated in macrophage and mouse infection models^[3]. GP63, or leishmanolysin, represents a separate virulence factor; targeted deletion in L. major identified GP63 as required for full parasite virulence^[4]. In macrophage biology, GP63 influences antimicrobial functions and alters signaling pathways that regulate microbicidal responses^[5]. For experimental applications, intracellular amastigote assays provide a clinically relevant drug-screening model, whereas promastigote screens are easier to automate but can miss active compounds^[6].