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Journal Article

In-depth quantitative proteomics uncovers specie-specific metabolic programs in Leishmania (Viannia) species


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

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Pinho, N., Wiśniewski, J. R., Dias-Lopes, G., Saboia-Vahia, L., Souza Bombaca, A. C., Mesquita-Rodrigues, C., et al. (2020). In-depth quantitative proteomics uncovers specie-specific metabolic programs in Leishmania (Viannia) species. PLoS Neglected Tropical Diseases, 14(8): e0008509. doi:10.1371/journal.pntd.0008509.

Cite as: http://hdl.handle.net/21.11116/0000-0007-1720-B
Author summary Leishmania braziliensis,L.panamensis, andL.guyanensisare responsible for most of the cases of tegumentary leishmaniasis (TL) in the Americas. These species are associated with a variety of clinical manifestations of TL ranging from self-healing localized cutaneous lesions to disseminated and mucocutaneous presentations that may result in severe oropharyngeal mutilation. Here, we report a comprehensive quantitative comparison of the proteome of those species. Assessment of absolute titers of similar to 7000 proteins revealed a very clear differentiation among them. Significant differences in energy metabolism, membrane proteins, transporters, and lipids are contributing for species-specific traits and provide rich substrate for exploring new molecules for diagnosing purposes. Leishmaniaspecies are responsible for a broad spectrum of diseases, denominated Leishmaniasis, affecting over 12 million people worldwide. During the last decade, there have been impressive efforts for sequencing the genome of most of the pathogenicLeishmaniaspp. as well as hundreds of strains, but large-scale proteomics analyses did not follow these achievements and theLeishmaniaproteome remained mostly uncharacterized. Here, we report a comprehensive comparative study of the proteomes of strains representingL.braziliensis,L.panamensisandL.guyanensisspecies. Proteins extracted by SDS-mediated lysis were processed following the multi-enzyme digestion-filter aided sample preparation (FASP) procedure and analysed by high accuracy mass spectrometry. "Total Protein Approach" and "Proteomic Ruler" were applied for absolute quantification of proteins. Principal component analysis demonstrated very high reproducibility among biological replicates and a very clear differentiation of the three species. Our dataset comprises near 7000 proteins, representing the most completeLeishmaniaproteome yet known, and provides a comprehensive quantitative picture of the proteomes of the three species in terms of protein concentration and copy numbers. Analysis of the abundance of proteins from the major energy metabolic processes allow us to highlight remarkably differences among the species and suggest that these parasites depend on distinct energy substrates to obtain ATP. WhereasL.braziliensisrelies the more on glycolysis,L.panamensisandL.guyanensisseem to depend mainly on mitochondrial respiration. These results were confirmed by biochemical assays showing opposite profiles for glucose uptake and O(2)consumption in these species. In addition, we provide quantitative data about different membrane proteins, transporters, and lipids, all of which contribute for significant species-specific differences and provide rich substrate for explore new molecules for diagnosing purposes. Data are available via ProteomeXchange with identifier PXD017696.