ArticleAntimicrobial agents and chemotherapy2013
A new ABC half-transporter in Leishmania major is involved in resistance to antimony.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 74 citations in OpenAlex.
- LABCG1 AffectsACS infectious diseases · 2026Article
- Heme limitation induces LHR2, an essential gene for Leishmania pathogenesis.PLoS pathogens · 2026Article
- Insights into drug resistance inADMET & DMPK · 2026Review
- Isolation and Identification of Highly Sb-Resistant Rhodotorula glutinis Strain J5 and its Mechanism of Resistance to Sb(III).Current microbiology · 2024Review
- Recent Advances in Chemotherapeutics for Leishmaniasis: Importance of the Cellular Biochemistry of the Parasite and Its Molecular Interaction with the Host.Pathogens (Basel, Switzerland) · 2023Review
- Global distribution of treatment resistance gene markers for leishmaniasis.Journal of clinical laboratory analysis · 2022Review
- The role of ATP-binding cassette transporter genes expression in treatment failure cutaneous leishmaniasis.AMB Express · 2022Article
- Antileishmanial Drug Discovery and Development: Time to Reset the Model?Microorganisms · 2021Review
- Comparative analysis of the transcriptional responses of five Leishmania species to trivalent antimony.Parasites & vectors · 2021Article
- Glutathione-coordinated metal complexes as substrates for cellular transporters.Metallomics : integrated biometal science · 2021Review
- Nanotechnology based solutions for anti-leishmanial impediments: a detailed insight.Journal of nanobiotechnology · 2021Review
- Insights intoVeterinary sciences · 2021Review
- A Critical Review of Resistance and Oxidation Mechanisms of Sb-Oxidizing Bacteria for the Bioremediation of Sb(III) Pollution.Frontiers in microbiology · 2021Review
- LmjF.22.0810 fromBiomedicines · 2020Article
- Using FluoZin-3 and fura-2 to monitor acute accumulation of free intracellular CdBiometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2019Article
- Dependence ofJournal of parasitic diseases : official organ of the Indian Society for Parasitology · 2019Review
- Protean permeases: Diverse roles for membrane transport proteins in kinetoplastid protozoa.Molecular and biochemical parasitology · 2019Review
- Genomic and transcriptomic alterations in Leishmania donovani lines experimentally resistant to antileishmanial drugs.International journal for parasitology. Drugs and drug resistance · 2018Article
- Increased thiol levels in antimony-resistant Leishmania infantum isolated from treatment-refractory visceral leishmaniasis in Brazil.Memorias do Instituto Oswaldo Cruz · 2018Article
- Drug resistance and treatment failure in leishmaniasis: A 21st century challenge.PLoS neglected tropical diseases · 2017Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The characterization of ABCI4, a new intracellular ATP-binding cassette (ABC) half-transporter in Leishmania major, is described. We show that ABCI4 is involved in heavy metal export, thereby conferring resistance to Pentostam, to Sb(III), and to As(III) and Cd(II). Parasites overexpressing ABCI4 showed a lower mitochondrial toxic effect of antimony by decreasing reactive oxygen species production and maintained higher values of both the mitochondrial electrochemical potential and total ATP levels with respect to controls. The ABCI4 half-transporter forms homodimers as determined by a coimmunoprecipitation assay. A combination of subcellular localization studies under a confocal microscope and a surface biotinylation assay using parasites expressing green fluorescent protein- and FLAG-tagged ABCI4 suggests that the transporter presents a dual localization in both mitochondria and the plasma membrane. Parasites overexpressing ABCI4 present an increased replication in mouse peritoneal macrophages. We have determined that porphyrins are substrates for ABCI4. Consequently, the overexpression of ABCI4 confers resistance to some toxic porphyrins, such as zinc-protoporphyrin, due to the lower accumulation resulting from a significant efflux, as determined using the fluorescent zinc-mesoporphyrin, a validated heme analog. In addition, ABCI4 has a significant ability to efflux thiol after Sb(III) incubation, thus meaning that ABCI4 could be considered to be a potential thiol-X-pump that is able to recognize metal-conjugated thiols. In summary, we have shown that this new ABC transporter is involved in drug sensitivity to antimony and other compounds by efflux as conjugated thiol complexes.
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