ArticlePLoS neglected tropical diseases2015
Fitness and Phenotypic Characterization of Miltefosine-Resistant Leishmania major.
Article in PLoS neglected tropical diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Evaluation of Beauvericin's activity and mode of action against all life stages ofFrontiers in cellular and infection microbiology · 2025Article
- ABC transporter inhibition by beauvericin partially overcomes drug resistance inAntimicrobial agents and chemotherapy · 2024Article
- Unmasking the Mechanism behind Miltefosine: Revealing the Disruption of Intracellular CaBiomolecules · 2024Review
- Genomic Insight of Leishmania Parasite: In-Depth Review of Drug Resistance Mechanisms and Genetic Mutations.ACS omega · 2024Review
- Systematic Review of Treatment Failure and Clinical Relapses in Leishmaniasis from a Multifactorial Perspective: Clinical Aspects, Factors Associated with the Parasite and Host.Tropical medicine and infectious disease · 2023Review
- Amphotericin B resistance correlates with increased fitnessFrontiers in microbiology · 2023Article
- Article
- Insights from Leishmania (Viannia) guyanensis in vitro behavior and intercellular communication.Parasites & vectors · 2021Article
- Miltefosine enhances infectivity of a miltefosine-resistant Leishmania infantum strain by attenuating its innate immune recognition.PLoS neglected tropical diseases · 2021Article
- LmjF.22.0810 fromBiomedicines · 2020Article
- Antileishmanial Aminopyrazoles: Studies into Mechanisms and Stability of Experimental Drug Resistance.Antimicrobial agents and chemotherapy · 2020Article
- Impact of clinically acquired miltefosine resistance by Leishmania infantum on mouse and sand fly infection.International journal for parasitology. Drugs and drug resistance · 2020Article
- Phenotypic adaptations of Leishmania donovani to recurrent miltefosine exposure and impact on sand fly infection.Parasites & vectors · 2020Article
- Effectiveness of Core-Shell Nanofibers Incorporating Amphotericin B by Solution Blow Spinning AgainstFrontiers in bioengineering and biotechnology · 2020Article
- An Overview of Drug Resistance in Protozoal Diseases.International journal of molecular sciences · 2019Review
- Need for sustainable approaches in antileishmanial drug discovery.Parasitology research · 2019Review
- Leishmania parasitophorous vacuole membranes display phosphoinositides that create conditions for continuous Akt activation and a target for miltefosine in Leishmania infections.Cellular microbiology · 2018Article
- Development of Thiophene Compounds as Potent Chemotherapies for the Treatment of Cutaneous Leishmaniasis Caused byMolecules (Basel, Switzerland) · 2018Article
- Induction of allopurinol resistance in Leishmania infantum isolated from dogs.PLoS neglected tropical diseases · 2017Article
- Different Mutations in a P-type ATPase Transporter in Leishmania Parasites are Associated with Cross-resistance to Two Leading Drugs by Distinct Mechanisms.PLoS neglected tropical diseases · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trypanosomatid parasites of the genus Leishmania are the causative agents of leishmaniasis, a neglected tropical disease with several clinical manifestations. Leishmania major is the causative agent of cutaneous leishmaniasis (CL), which is largely characterized by ulcerative lesions appearing on the skin. Current treatments of leishmaniasis include pentavalent antimonials and amphotericin B, however, the toxic side effects of these drugs and difficulty with distribution makes these options less than ideal. Miltefosine (MIL) is the first oral treatment available for leishmaniasis. Originally developed for cancer chemotherapy, the mechanism of action of MIL in Leishmania spp. is largely unknown. While treatment with MIL has proven effective, higher tolerance to the drug has been observed, and resistance is easily developed in an in vitro environment. Utilizing stepwise selection we generated MIL-resistant cultures of L. major and characterized the fitness of MIL-resistant L. major. Resistant parasites proliferate at a comparable rate to the wild-type (WT) and exhibit similar apoptotic responses. As expected, MIL-resistant parasites demonstrate decreased susceptibility to MIL, which reduces after the drug is withdrawn from culture. Our data demonstrate metacyclogenesis is elevated in MIL-resistant L. major, albeit these parasites display attenuated in vitro and in vivo virulence and standard survival rates in the natural sandfly vector, indicating that development of experimental resistance to miltefosine does not lead to an increased competitive fitness in L. major.
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