title: Leishmania parasites possess a platelet-activating factor acetylhydrolase important for virulence.
abstract: Leishmania parasites are intracellular protozoans capable of salvaging and remodeling lipids from the host. To understand the role of lipid metabolism in Leishmania virulence, it is necessary to characterize the enzymes involved in the uptake and turnover of phospholipids. This study focuses on a putative phospholipase A2 (PLA2)/platelet-activating factor acetylhydrolase (PAF-AH) in Leishmania major. In mammals, PAF-AH is a subgroup of PLA2 catalyzing the hydrolysis/inactivation of platelet-activating factor (PAF), a potent mediator of many leukocyte functions. By immunofluorescence microscopy, L. major PLA2/PAF-AH is predominantly localized in the ER. While wild type L. major parasites are able to hydrolyze PAF, this activity is completely absent in the PLA2/PAF-AH-null mutants. Meanwhile, deletion of PLA2/PAF-AH had no significant effect on the turnover of common glycerophospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol. PLA2/PAF-AH is not required for the growth of L. major parasites in culture, or the production of GPI-anchored virulence factors. Nonetheless, it does play a key role in the mammalian host as the PLA2/PAF-AH null mutants exhibit attenuated virulence in BALB/c mice. In conclusion, these data suggest that Leishmania parasites possess a functional PAF-AH and the degradation of PAF or PAF-like lipids is an important step in infection.
authors.affiliation: Department of Biological Sciences, Texas Tech University, Lubbock, TX 79409, USA.
authors.forename: Mattie C
authors.initials: MC
authors.lastname: Pawlowic
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000201:enzymology; D017353:Gene Deletion; D018320:Leishmania major / Q000201:enzymology* / Q000254:growth & development / Q000472:pathogenicity*; D016773:Leishmaniasis, Cutaneous / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D010743:Phospholipids / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism*; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D010743:Phospholipids; D010972:Platelet Activating Factor; D037521:Virulence Factors; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase