title: LABCG2, a new ABC transporter implicated in phosphatidylserine exposure, is involved in the infectivity and pathogenicity of Leishmania.
abstract: Leishmaniasis is a neglected disease produced by the intracellular protozoan parasite Leishmania. In the present study, we show that LABCG2, a new ATP-binding cassette half-transporter (ABCG subfamily) from Leishmania, is involved in parasite virulence. Down-regulation of LABCG2 function upon expression of an inactive mutant version of this half-transporter (LABCG2(K/M)) is shown to reduce the translocation of short-chain analogues of phosphatidylserine (PS). This dominant-negative phenotype is specific for the headgroup of the phospholipid, as the movement of phospholipid analogues of phosphatidylcholine, phosphatidylethanolamine or sphingomyelin is not affected. In addition, promastigotes expressing LABCG2(K/M) expose less endogenous PS in the stationary phase than control parasites. Transient exposure of PS at the outer leaflet of the plasma membrane is known to be one of the mechanisms used by Leishmania to infect macrophages and to silence their immune response. Stationary phase/metacyclic promastigotes expressing LABCG2(K/M) are less infective for macrophages and show decreased pathogenesis in a mouse model of cutaneous leishmaniasis. Thus, mice infected with parasites expressing LABCG2(K/M) did not develop any lesion and showed significantly lower inflammation and parasite burden than mice infected with control parasites. Our results indicate that LABCG2 function is required for the externalization of PS in Leishmania promastigotes, a process that is involved in the virulence of the parasite.
authors: Instituto de Parasitología y Biomedicina "López-Neyra", CSIC, (IPBLN-CSIC), Parque Tecnológico de Ciencias de la Salud, Armilla, Granada, Spain.
authors: Jenny
authors: J
authors: Campos-Salinas
authors: David
authors: D
authors: León-Guerrero
authors: Elena
authors: E
authors: González-Rey
authors: Mario
authors: M
authors: Delgado
authors: Santiago
authors: S
authors: Castanys
authors: José M
authors: JM
authors: Pérez-Victoria
authors: Francisco
authors: F
authors: Gamarro
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005260:Female; D007891:Leishmania / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D018320:Leishmania major / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D051379:Mice; D008807:Mice, Inbred BALB C; D010718:Phosphatidylserines / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D010718:Phosphatidylserines; D015800:Protozoan Proteins
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