LeishMANIAdb: a comparative resource for Leishmania proteins

Abstract

Leishmaniasis is a detrimental disease causing serious changes in quality of life and some forms can lead to death. The disease is spread by the parasite Leishmania transmitted by sandfly vectors and their primary hosts are vertebrates including humans. The pathogen penetrates host cells and secretes proteins (the secretome) to repurpose cells for pathogen growth and to alter cell signaling via host–pathogen protein–protein interactions). Here, we present LeishMANIAdb, a database specifically designed to investigate how Leishmania virulence factors may interfere with host proteins. Since the secretomes of different Leishmania species are only partially characterized, we collated various experimental evidence and used computational predictions to identify Leishmania secreted proteins to generate a user-friendly unified web resource allowing users to access all information available on experimental and predicted secretomes. In addition, we manually annotated host–pathogen interactions of 211 proteins and the localization/function of 3764 transmembrane (TM) proteins of different Leishmania species. We also enriched all proteins with automatic structural and functional predictions that can provide new insights in the molecular mechanisms of infection. Our database may provide novel insights into Leishmania host–pathogen interactions and help to identify new therapeutic targets for this neglected disease. Database URL https://leishmaniadb.ttk.hu/

Linear motifs regulating protein secretion, sorting and autophagy in Leishmania parasites are diverged with respect to their host equivalents

“…While the known Leishmania signal peptides (SPs) do have a broad similarity to generic eukaryotic signals, they more closely resemble bacterial type II signal peptides in several aspects, such as their amino acid content. For a concise analysis, we collected SPs predicted by SignalP6 [ 32 ] in LeishMANIAdb [ 30 ] and in SwissProt [ 33 ]. When examining their hydrophobic core, we noticed that SPs in Leishmania strongly prefer small hydrophobic amino acids, resulting in higher alanine (relative frequency (r.f.…”

“…braziliensis , L . donovani) from LeishMANIAdb 1.0 [ 30 ], while SwissProt 2023_2 [ 33 ] was also used as a reference. Signal peptides were predicted using SignalP6.0 [ 32 ].…”

“…While kinetoplastids appear to possess secretory signal peptides resembling other eukaryotes and bacteria [ 28 , 29 ], as well as a fairly canonical ER physiology and autophagy, we sought to explore if these systems do match with those of higher eukaryotes at a molecular level. During our analysis, we made extensive use of the LeishMANIAdb [ 30 ] database developed by our group. Our studies suggest that while these systems have an ancient eukaryotic heritage, they heavily diverged in Kinetoplastids and can be difficult to identify by comparative sequence analysis approaches.…”

Exploring Leishmania linear motifs directing protein secretion, sorting and autophagy

“…While the known Leishmania signal peptides (SPs) do have a broad similarity to generic eukaryotic signals, they more closely resemble bacterial type II signal peptides in several aspects, such as their amino acid content. For a concise analysis, we collected SPs predicted by SignalP6 10 in LeishMANIAdb 8 and in SwissProt 11 . When examining their hydrophobic region, we noticed that SPs in Leishmania strongly prefer small hydrophobic amino acids, resulting in higher alanine and valine and lower leucine and phenylalanine content, compared to other eukaryotes (Figure 1/A, Supplementary Table 1).…”