Format

Send to

Choose Destination
See comment in PubMed Commons below
PLoS Negl Trop Dis. 2013 Apr 25;7(4):e2179. doi: 10.1371/journal.pntd.0002179. Print 2013.

LABCG2, a new ABC transporter implicated in phosphatidylserine exposure, is involved in the infectivity and pathogenicity of Leishmania.

Author information

1
Instituto de Parasitología y Biomedicina "López-Neyra", CSIC, (IPBLN-CSIC), Parque Tecnológico de Ciencias de la Salud, Armilla, Granada, Spain.

Erratum in

  • PLoS Negl Trop Dis. 2013 Jun;7(6). doi:10.1371/annotation/6a3b1d53-4e80-45a9-8fab-f3fb56a134de.

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.

PMID:
23638200
PMCID:
PMC3636091
DOI:
10.1371/journal.pntd.0002179
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Support Center