Unravelling the proteomic signature of extracellular vesicles released by drug-resistant Leishmania infantum parasites

摘要

Visceral leishmaniasis is a life-threatening disease caused by Leishmania infantum parasites, which are transmitted by sand flies. In the absence of vaccines, current control of this disease is based on chemotherapy, which is comprised of a very limited arsenal threatened by the emergence and spread of drug-resistant strains. In the shadow of growing concern and treatment failure due to resistance, the characterization of extracellular vesicles (EVs) released by drug-resistant L. infantum parasites could shed some light on the complex nature of drug resistance in Leishmania and increase our understanding of the biology of the parasite. EVs are vesicles secreted by all eukaryotic cells whose contents (proteins, DNA/RNAs, lipids) vary as a function of their cellular origin. Our results demonstrate for the first time that EVs released by drug-resistant parasites are enriched in unique protein markers that reflect the drug-resistance mechanisms involved in the survival of parental cells. These unique proteins included several virulence and transcription factors, as well as drug-resistance genes; this offers a potential benefit for drug-resistant parasites in terms of parasite-to-parasite communication and host-parasite interactions. Collectively, our initial results could serve as a jumping-off point for the future development of novel EV-based diagnostic tools for the detection and appraisal of antimicrobial-resistant Leishmania populations.