Identification of potential novel proteomic markers of Leishmania spp.-derived exosomes

Alonso da Silva Lira Filho; Andrea Lafleur; Marcelo Marcet-Palacios; Martin Olivier

doi:10.3389/fcimb.2024.1354636

Identification of potential novel proteomic markers of Leishmania spp.-derived exosomes

Front Cell Infect Microbiol. 2024 Feb 19:14:1354636. doi: 10.3389/fcimb.2024.1354636. eCollection 2024.

Authors

Alonso da Silva Lira Filho^{1

2}, Andrea Lafleur^{1

2}, Marcelo Marcet-Palacios^{3

4}, Martin Olivier^{1

2}

Affiliations

¹ Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada.
² Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montréal, QC, Canada.
³ Department of Medicine, Alberta Respiratory Centre, University of Alberta, Edmonton, AB, Canada.
⁴ Department of Biological Sciences Technology, Laboratory Research and Biotechnology, Northern Alberta Institute of Technology, Edmonton, AB, Canada.

Abstract

Introduction: Extracellular vesicles (EVs) are heterogenous cell-derived membrane-bound structures which can be subdivided into three distinct classes according to distinct morphological characteristics, cellular origins, and functions. Small EVs, or exosomes, can be produced by the protozoan parasite Leishmania through the evolutionarily conserved ESCRT pathway, and act as effectors of virulence and drivers of pathogenesis within mammalian hosts. Techniques for the identification of EVs of non-mammalian origin, however, remain inaccurate in comparison to their well-characterized mammalian counterparts. Thus, we still lack reliable and specific markers for Leishmania-derived exosomes, which poses a significant challenge to the field.

Methods: Herein, we utilized serial differential ultracentrifugation to separate Leishmania-derived EV populations into three distinct fractions. Nanoparticle tracking analysis and transmission electron microscopy were used to validate their morphological characteristics, and bioinformatic analysis of LC-MS/MS proteomics corroborated cellular origins and function.

Discussion: Proteomic data indicated potential novel proteic markers of Leishmania-derived exosomes, including proteins involved in endosomal machinery and the ESCRT pathway, as well as the parasitic phosphatase PRL-1. Further investigation is required to determine the specificity and sensitivity of these markers.

Keywords: Leishmania; cutaneous leishmaniasis; exosomes; extracellular vesicles; proteomics.

MeSH terms

Animals
Chromatography, Liquid
Endosomal Sorting Complexes Required for Transport
Exosomes*
Leishmania*
Mammals
Proteomics
Tandem Mass Spectrometry

Substances

Endosomal Sorting Complexes Required for Transport

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by the Canadian Institutes of Health Research (CIHR, grant numbers PJT-159765 and ER1-143489). AL received an M.Sc. studentship through the Fonds de Recherches du Québecen Santé (FRQS) Graduate Student Scholarship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.