2024-03-29T14:13:10Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/800272021-05-24T10:40:41Zcom_10261_64com_10261_1col_10261_317
2013-07-22T11:40:24Z
urn:hdl:10261/80027
LABCG2, a New ABC Transporter Implicated in Phosphatidylserine Exposure, Is Involved in the Infectivity and Pathogenicity of Leishmania
Campos-Salinas, Jenny
León-Guerrero, D.
González-Rey, Elena
Delgado, M.
Castanys, Santiago
Pérez-Victoria, J. M.
Gamarro, Francisco
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 (LABCG2K/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 LABCG2K/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 LABCG2K/M are less infective for macrophages and show decreased pathogenesis in a mouse model of cutaneous leishmaniasis. Thus, mice infected with parasites expressing LABCG2K/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. © 2013 Campos-Salinas et al.
2013-07-22T11:40:24Z
2013-07-22T11:40:24Z
2013
2013-07-22T11:40:24Z
artículo
PLoS Neglected Tropical Diseases 7 (2013)
http://hdl.handle.net/10261/80027
10.1371/journal.pntd.0002179
23638200
eng
openAccess