Publication
Title
Impact of clinically acquired miltefosine resistance by Leishmania infantum on mouse and sand fly infection
Author
Abstract
Objectives This study evaluated the implications of clinically acquired miltefosine resistance (MIL-R) by assessing virulence in mice and sand flies to reveal the potential of MIL-R strains to circulate. Methods Experimental infections with the MIL-R clinical Leishmania infantum isolate MHOM/FR/2005/LEM5159, having a defect in the LiROS3 subunit of the MIL-transporter, and its syngeneic experimentally reconstituted MIL-S counterpart (LEM5159LiROS3) were performed in BALB/c mice and Lutzomyia longipalpis and Phlebotomus perniciosus sand flies. In mice, the amastigote burdens in liver and spleen were compared microscopically using Giemsa smears and by bioluminescent imaging. During the sand fly infections, the percentage of infected flies, parasite load, colonization of the stomodeal valve and metacyclogenesis were evaluated. The stability of the MIL-R phenotype after sand fly and mouse passage was determined as well. Results The fitness of the MIL-R strain differed between the mouse and sand fly infection model. In mice, a clear fitness loss was observed compared to the LiROS3-reconstituted susceptible strain. This defect could be rescued by episomal reconstitution with a wildtype LiROS3 copy. However, this fitness loss was not apparent in the sand fly vector, resulting in metacyclogenesis and efficient colonization of the stomodeal valve. Resistance was stable after passage in both sand fly and mouse. Conclusion The natural MIL-R strain is significantly hampered in its ability to multiply and cause a typical visceral infection pattern in BALB/c mice. However, this LiROS3-deficient strain efficiently produced mature infections and metacyclic promastigotes in the sand fly vector highlighting the transmission potential of this particular MIL-R clinical Leishmania strain.
Language
English
Source (journal)
International Journal for Parasitology: Drugs and Drug Resistance
Publication
2020
ISSN
2211-3207
DOI
10.1016/J.IJPDDR.2020.04.004
Volume/pages
13 (2020) , p. 16-21
ISI
000556674900003
Pubmed ID
32388220
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Project info
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.
Identifying factors involved in miltefosine or amphotericin B treatment failure in visceral leishmaniasis.
The role of parasite sanctuary sites and interaction with Kupffer cells in treatment failure of Visceral Leishmaniasis
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
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 07.05.2020
Last edited 02.10.2024
To cite this reference