3 years ago

ABCI3, a new mitochondrial ABC transporter from Leishmania major involved in susceptibility to antimonials and infectivity.

Gamarro, Manzano, Arcari
We have identified and characterized ABCI3 as a new mitochondrial ABC transporter from Leishmania major. Localization studies using confocal microscope, surface biotinylation assay and trypsin digestion after digitonin permeabilization suggested that ABCI3 presents a dual localization in both mitochondria and plasma membrane. Using single-knock out parasites for ABCI3 (ABCI3(+/-) ), we provided evidence that ABCI3 is directly involved in Sb(III) and metal ions susceptibility. Attempts to obtain double knock-out parasites for ABCI3 were unsuccessful, suggesting that ABCI3 could be an essential gene in L. majorABCI3(+/-) promastigotes were 5-fold more resistant to Sb(III), while ABCI3(+/-) amastigotes were approximately 2-fold more resistant to Sb(V) This resistant phenotype was associated with a decreased Sb(III) accumulation due to a decreased Sb(III) uptake. ABCI3(+/-) parasites presented higher ATP levels and generated less mitochondrial superoxide after Sb(III) incubation. Finally, we have observed that ABCI3(+/-) parasites showed a slightly higher infection capacity than wild-type and add-back ABCI3(+/-):3xFABCI3 parasites; however, after 72 h the number of ABC3(+/-) intracellular parasites per macrophage increased significantly. Our results show that ABCI3 is responsible for Sb(III) transport inside mitochondria, where it would contribute to enhance the general toxic effects caused by Sb(III) To our knowledge, ABCI3 is the first ABC transporter which is involved in susceptibility towards antimony, conferring Sb(III) resistance to parasites when partially deleted.

Publisher URL: http://doi.org/10.1128/AAC.01115-17

DOI: 10.1128/AAC.01115-17

You might also like
Never Miss Important Research

Researcher is an app designed by academics, for academics. Create a personalised feed in two minutes.
Choose from over 15,000 academics journals covering ten research areas then let Researcher deliver you papers tailored to your interests each day.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.