**5. Proteophosphoglycan (PPG)**

*Leishmania* expresses several types from proteophosphoglycans (PPGs). Some of PPGs are secreted and others found on surface of amastigotes and promastigotes [80]. PPGs are a large group from widely glycosylated proteins, have some unique features [81]. It is produce by both two parasite stages, is found on the parasite surface, Golgi, lysosome and flagellar pocket [53]. There are number of PPGs types, include filamentous proteophospho-glycan (fPPG) and GPIanchored membranous proteophosphoglycan (mPPG), all of that are originally in stages of promastigotes within sandfly vector, there is also non-filamentous proteophosphoglycan (aPPG) which is a major product of amastigotes in mammalian host [82–84]. The ppg1 gene encodes membrane-bound PPG, and secreted nonfilamentous PPG is encoded by ppg2 [85], while ppg3 gene is encode filamentous proteophosphoglycan [86]. Compositional analysis observed PPG contains 67% glycan, 28% protein and 5% phosphate. PPG is composed from repeating units of PGs that attach to protein backbone [81]. PG molecules are either connected to cell surface via GPI-lipid anchor, or secreted as protein-containing phosphoglycans [51]. PPG is proved to bind to macrophage receptors in order to facilitates parasite invasion, this may be explaining that PPG play an early role in infection and prevalence [53, 87, 88] are suggest possibilities of PPG in drug resistant mechanisms and PPG abundance of *L. donovani* is as evidence for resistant clinical isolates. PPG- null mutant *L. major* are more sensitive and less virulent to complement-lysis. In infected mice, not develop lesions in PPG- null mutant parasites [82]. Metacyclic promastigotes in sandfly midgut secrete fPPG which condenses to promastigote secretory gel (PSG), to formation a biological plug that block the anterior midgut, this is oblige sandfly to disgorge parasites though blood-feeding [89]. PSG is largest molecule that secretes by promastigotes within sandfly gut. Also, it is support both macrophage assemblage and infection [90]. Inside infected macrophages, amastigotes secrete aPPG which can reach to very high concentrations [90]. The membrane-bound PPG may play a direct important role in host–parasite interactions [90]. It is found on the surface of amastigotes and promastigotes [91]. Within macrophage, believed that aPPG is contribute in

formation of parasitophorous vacuole, this protects infection in the mammalian cells, also PPG may contribute binding of *Leishmania* to host-cells and may be modulate biology of infected macrophage in the early infection [83].
