Proteomic Analysis of the Promastigote Secretome of Seven Leishmania Species

Abstract

Leishmaniasis is one of the most impactful parasitic diseases worldwide, endangering the lives of 1 billion people every year. There are 20 different species of Leishmania able to infect humans, causing cutaneous (CL), visceral (VL), and/or mucocutaneous leishmaniasis (MCL). Leishmania parasites are known to secrete a plethora of proteins to establish infection and modulate the host's immune system. In this study, we analyzed using tandem mass spectrometry the total protein content of the secretomes produced by promastigote forms from seven Leishmania species grown in serum-free in vitro cultures. The core secretome shared by all seven Leishmania species corresponds to up to one-third of total secreted proteins, suggesting conserved mechanisms of adaptation to the vertebrate host. The relative abundance confirms the importance of known virulence factors and some proteins uniquely present in CL-or VL-causing species and may provide further insight regarding their pathogenesis. Bioinformatic analysis showed that most proteins were secreted via unconventional mechanisms, with an important role for vesiclebased secretion for all species. Gene Ontology annotation and enrichment analyses showed a high level of functional conservation among species. This study contributes to the current knowledge on the biological significance of differently secreted proteins and provides new information on the correlation of Leishmania secretome to clinical outcomes and species-specific pathogenesis.

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“…These proteins were also abundant in Leishmania spp. exoproteome except NADPH oxidase (Pissarra et al ., 2022). Furthermore, we compared 193 L. passim exoproteome proteins and 306 exoproteome proteins shared between seven Leishmania spp.…”

“…Finally, clusterProfiler (Yu et al ., 2012) of the R software package was used to perform GO and KEGG pathway enrichment analyses. We compared 193 L. passim exoproteome proteins with 306 exoproteome proteins common between seven Leishmania spp (Pissarra et al ., 2022) using reciprocal BLASTP and 67 protein pairs showed the e-value lower than 6E-03. Among them, 55 were considered homologs with an e-value lower than 1E-50.…”

“…(A) A Venn diagram to indicate 55 proteins are shared between 193 L. passim exoproteome proteins and 306 exoproteome proteins common with seven Leishmania spp. (Pissarra et al ., 2022). (B) Protein-protein interaction map of L. passim exoproteome predicted by STRING.…”

“…to enable the identification of proteins involved in parasite survival, pathogenesis, and other biologically relevant processes. Pissarra et al ., identified exoproteomes of seven Leishmania species and found the shared core set of proteins as well as the species-specific proteins (Pissarra et al ., 2022). These results suggest the exoproteome has both conserved functions to adapt to the host and specific roles related to species-specific pathogenesis.…”

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“…Later, in bioinformatics analysis, it was found that most of the proteins were secreted through an unconventional mechanism. The high preservation of the protein and its recognized function in the Leishmania secretome data sets further validate the recommended use of promastigote-secreted proteins as a generator for antigen discovery and the production of vaccines and drug targets [ 79 ].…”