Help Privacy Policy Disclaimer
  Advanced SearchBrowse




Journal Article

In-Depth Quantitative Proteomics Characterization of In Vitro Selected Miltefosine Resistance in Leishmania infantum


Wisniewski,  Jacek R.
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available

Saboia-Vahia, L., Cuervo, P., Wisniewski, J. R., Dias-Lopes, G., Pinho, N., Padron, G., et al. (2022). In-Depth Quantitative Proteomics Characterization of In Vitro Selected Miltefosine Resistance in Leishmania infantum. Proteomes, 10(2): 10. doi:10.3390/proteomes10020010.

Cite as: https://hdl.handle.net/21.11116/0000-000A-B216-4
Visceral leishmaniasis (VL) is a neglected disease caused by Leishmania parasites. Although significant morbidity and mortality in tropical and subtropical regions of the world are associated with VL, the low investment for developing new treatment measures is chronic. Moreover, resistance and treatment failure are increasing for the main medications, but the emergence of resistance phenotypes is poorly understood at the protein level. Here, we analyzed the development of resistance to miltefosine upon experimental selection in a L. infantum strain. Time to miltefosine resistance emergence was similar to six months and label-free quantitative mass-spectrometry-based proteomics analyses revealed that this process involves a remodeling of components of the membrane and mitochondrion, with significant increase in oxidative phosphorylation complexes, particularly on complex IV and ATP synthase, accompanied by increased energy metabolism mainly dependent on beta-oxidation of fatty acids. Proteins canonically involved in ROS detoxification did not contribute to the resistant process whereas sterol biosynthesis enzymes could have a role in this development. Furthermore, changes in the abundance of proteins known to be involved in miltefosine resistance such as ABC transporters and phospholipid transport ATPase were detected. Together, our data show a more complete picture of the elements that make up the miltefosine resistance phenotype in L. infantum.