Publication
Title
Phenotypic adaptations of Leishmania donovani to recurrent miltefosine exposure and impact on sand fly infection
Author
Abstract
Background Since the introduction of miltefosine (MIL) as first-line therapy in the kala-azar elimination programme in the Indian subcontinent, treatment failure rates have been increasing. Since parasite infectivity and virulence may become altered upon treatment relapse, this laboratory study assessed the phenotypic effects of repeated in vitro and in vivo MIL exposure. Methods Syngeneic Leishmania donovani lines either or not exposed to MIL were compared for drug susceptibility, rate of promastigote multiplication and metacyclogenesis, macrophage infectivity and behaviour in the sand fly vector, Lutzomyia longipalpis. Results Promastigotes of both in vitro and in vivo MIL-selected strains displayed a slightly reduced drug susceptibility that was associated with a reduced MIL-accumulation linked to a lower copy number (disomic state) of chromosome 13 harboring the miltefosine transporter (LdMT) gene. In vitro selected promastigotes showed a lower rate of metacyclogenesis whereas the in vivo derived promastigotes displayed a moderately increased growth rate. Repeated MIL exposure did neither influence the parasite load nor metacyclogenesis in the sand fly vector. Conclusions Recurrent in vitro and in vivo MIL exposure evokes a number of very subtle phenotypic and genotypic changes which could make promastigotes less susceptible to MIL without attaining full resistance. These changes did not significantly impact on infection in the sand fly vector.
Language
English
Source (journal)
Parasites and vectors
Publication
2020
ISSN
1756-3305
DOI
10.1186/S13071-020-3972-Z
Volume/pages
13 :1 (2020) , 11 p.
Article Reference
96
ISI
000517327500002
Pubmed ID
32087758
Medium
E-only publicatie
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Project info
Dynamics and mechanisms of paromomycin and miltefosine drug-resistance in the protozoan parasite Leishmania.
The role of infiltrating immune cells in the aggresive phenotype of inflammatory breast cancer and possible new (immuno)therapeutic targets.
Veterinary and human parasitology.
Towards new concepts in anti-Leishmania treatment by modifying the interplay between sand fly transmitted parasites and the host innate immune system
Infla-Med: Fundamental and translational research into targets for the treatment of inflammatory diseases.
The role of parasite sanctuary sites and interaction with Kupffer cells in treatment failure of Visceral Leishmaniasis
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 06.04.2020
Last edited 02.10.2024
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