ArticleThe Journal of antimicrobial chemotherapy2014
Leishmania panamensis infection and antimonial drugs modulate expression of macrophage drug transporters and metabolizing enzymes: impact on intracellular parasite survival.
Article in The Journal of antimicrobial chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- DNA Methylation in macrophages infected withEmerging microbes & infections · 2025Article
- Interplay of human macrophage response and natural resistance of infection by L. (V.) panamensis to pentavalent antimony.PLoS neglected tropical diseases · 2025Article
- Improved synthesis of deoxyalpinoid B and quantification of antileishmanial activity of deoxyalpinoid B and sulforaphane.Bioorganic & medicinal chemistry · 2023Article
- Macrophage metallothioneins participate in the antileishmanial activity of antimonials.Frontiers in parasitology · 2023Article
- Transcriptomic Analysis in Human Macrophages Infected with Therapeutic Failure Clinical Isolates ofACS infectious diseases · 2022Article
- Cytotoxicity of Essential OilMolecules (Basel, Switzerland) · 2021Article
- Immuno-pharmacokinetics of Meglumine Antimoniate in Patients With Cutaneous Leishmaniasis Caused by Leishmania (Viannia).Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Article
- Neutrophil Activation: Influence of Antimony Tolerant and Susceptible Clinical Strains ofFrontiers in cellular and infection microbiology · 2021Article
- A human xenobiotic nuclear receptor contributes to nonresponsiveness ofThe Journal of biological chemistry · 2018Article
- In Search of Biomarkers for Pathogenesis and Control of Leishmaniasis by Global Analyses ofFrontiers in cellular and infection microbiology · 2018Review
- Profiling gene expression of antimony response genes in Leishmania (Viannia) panamensis and infected macrophages and its relationship with drug susceptibility.Acta tropica · 2017Article
- Knockdown of Host Antioxidant Defense Genes Enhances the Effect of Glucantime on Intracellular Leishmania braziliensis in Human Macrophages.Antimicrobial agents and chemotherapy · 2017Article
- Local Delivery of the Toll-Like Receptor 9 Ligand CpG Downregulates Host Immune and Inflammatory Responses, Ameliorating Established Leishmania (Viannia) panamensis Chronic Infection.Infection and immunity · 2017Article
- Snapshot Profiling of the Antileishmanial Potency of Lead Compounds and Drug Candidates against Intracellular Leishmania donovani Amastigotes, with a Focus on Human-Derived Host Cells.Antimicrobial agents and chemotherapy · 2017Article
- Clinical and Parasitological Features of Patients with American Cutaneous Leishmaniasis that Did Not Respond to Treatment with Meglumine Antimoniate.PLoS neglected tropical diseases · 2016Observational
- Functional Validation of ABCA3 as a Miltefosine Transporter in Human Macrophages: IMPACT ON INTRACELLULAR SURVIVAL OF LEISHMANIA (VIANNIA) PANAMENSIS.The Journal of biological chemistry · 2016Article
- Simultaneous transcriptional profiling of Leishmania major and its murine macrophage host cell reveals insights into host-pathogen interactions.BMC genomics · 2015Article
- Ex vivo host and parasite response to antileishmanial drugs and immunomodulators.PLoS neglected tropical diseases · 2015Article
- A Multiplatform Metabolomic Approach to the Basis of Antimonial Action and Resistance in Leishmania infantum.PloS one · 2015Article
- Chronic arsenic exposure and microbial drug resistance.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
objectivesTreatment failure is multifactorial. Despite the importance of host cell drug transporters and metabolizing enzymes in the accumulation, distribution and metabolism of drugs targeting intracellular pathogens, their impact on the efficacy of antileishmanials is unknown. We examined the contribution of pharmacologically relevant determinants in human macrophages in the antimony-mediated killing of intracellular Leishmania panamensis and its relationship with the outcome of treatment with meglumine antimoniate.
methodsPatients with cutaneous leishmaniasis who failed (n = 8) or responded (n =8) to treatment were recruited. Gene expression profiling of pharmacological determinants in primary macrophages was evaluated by quantitative RT-PCR and correlated to the drug-mediated intracellular parasite killing. Functional validation was conducted through short hairpin RNA gene knockdown.
resultsSurvival of L. panamensis after exposure to antimonials was significantly higher in macrophages from patients who failed treatment. Sixteen macrophage drug-response genes were modulated by infection and exposure to meglumine antimoniate. Correlation analyses of gene expression and intracellular parasite survival revealed the involvement of host cell metallothionein-2A and ABCB6 in the survival of Leishmania during exposure to antimonials. ABCB6 was functionally validated as a transporter of antimonial compounds localized in both the cell and phagolysosomal membranes of macrophages, revealing a novel mechanism of host cell-mediated regulation of intracellular drug exposure and parasite survival within phagocytes.
conclusionsThese results provide insight into host cell mechanisms regulating the intracellular exposure of Leishmania to antimonials and variations among individuals that impact parasite survival. Understanding of host cell determinants of intracellular pharmacokinetics/pharmacodynamics opens new avenues to improved drug efficacy for intracellular pathogens.
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