An in silico functional annotation and screening of potential drug targets derived from Leishmania spp. hypothetical proteins identified by immunoproteomics

Chávez-Fumagalli, Miguel Á.; Schneider, Mônica Santos; Lage, Daniela P.; Machado-de-Ávila, Ricardo Andrez; Coelho, Eduardo Antônio Ferraz

doi:10.1016/j.exppara.2017.03.005

Cited by 17 publications

(7 citation statements)

References 96 publications

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“…Computational analysis in combination with immunoproteomic approaches has led to the screening and identification of new drug targets based on their localization and biological functions [165]. In silico approaches have also been proven to be efficacious in determining the serological significance of leishmanial antigens with tandem repeat domains [166].…”

Section: Modulation Of the Leishmania Proteome Profilementioning

confidence: 99%

“…In silico approaches have also been proven to be efficacious in determining the serological significance of leishmanial antigens with tandem repeat domains [166]. A combination of immunoproteomic approaches along with in silico predictions led to the search for new drug targets according to their localization and biological functions [165].…”

Section: Modulation Of the Leishmania Proteome Profilementioning

confidence: 99%

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UnderstandingLeishmaniaparasites through proteomics and implications for the clinic

Sundar

Singh

2018

Expert Review of Proteomics

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Leishmania spp. are causative agents of leishmaniasis, a broad-spectrum neglected vector-borne disease. Genomic and transcriptional studies are not capable of solving intricate biological mysteries, leading to the emergence of proteomics, which can provide insights into the field of parasite biology and its interactions with the host. Areas covered: The combination of genomics and informatics with high throughput proteomics may improve our understanding of parasite biology and pathogenesis. This review analyses the roles of diverse proteomic technologies that facilitate our understanding of global protein profiles and definition of parasite development, survival, virulence and drug resistance mechanisms for disease intervention. Additionally, recent innovations in proteomics have provided insights concerning the drawbacks associated with conventional chemotherapeutic approaches and Leishmania biology, host-parasite interactions and the development of new therapeutic approaches. Expert commentary: With progressive breakthroughs in the foreseeable future, proteome profiles could provide target molecules for vaccine development and therapeutic intervention. Furthermore, proteomics, in combination with genomics and informatics, could facilitate the elimination of several diseases. Taken together, this review provides an outlook on developments in Leishmania proteomics and their clinical implications.

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Section: Modulation Of the Leishmania Proteome Profilementioning

confidence: 99%

Section: Modulation Of the Leishmania Proteome Profilementioning

confidence: 99%

UnderstandingLeishmaniaparasites through proteomics and implications for the clinic

Sundar

Singh

2018

Expert Review of Proteomics

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“…In the amastigote extract, four hypothetical and 17 known proteins were identified. From these, virulence factors, such as leucine-rich repeat protein (Mukherjee et al ., 2016), diagnosis markers, such as enolase (Duarte et al ., 2017), vaccine candidates, such as eukaryotic initiation factor 4a (Maspi et al ., 2015), and drug targets, such as calpain-like cysteine peptidase (Chávez-Fumagalli et al ., 2017) were recognized.…”

Section: Resultsmentioning

confidence: 99%

Screening diagnostic candidates fromLeishmania infantumproteins for human visceral leishmaniasis using an immunoproteomics approach

et al. 2019

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There is no suitable vaccine against human visceral leishmaniasis (VL) and available drugs are toxic and/or present high cost. In this context, diagnostic tools should be improved for clinical management and epidemiological evaluation of disease. However, the variable sensitivity and/or specificity of the used antigens are limitations, showing the necessity to identify new molecules to be tested in a more sensitive and specific serology. In the present study, an immunoproteomics approach was performed in Leishmania infantum promastigotes and amastigotes employing sera samples from VL patients. Aiming to avoid undesired cross-reactivity in the serological assays, sera from Chagas disease patients and healthy subjects living in the endemic region of disease were also used in immunoblottings. The most reactive spots for VL samples were selected, and 29 and 21 proteins were identified in the promastigote and amastigote extracts, respectively. Two of them, endonuclease III and GTP-binding protein, were cloned, expressed, purified and tested in ELISA experiments against a large serological panel, and results showed high sensitivity and specificity values for the diagnosis of disease. In conclusion, the identified proteins could be considered in future studies as candidate antigens for the serodiagnosis of human VL.

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“…In addition, among these candidates, seven were identified as hypothetical proteins [ 17 ]. To predict their subcellular localization and functional annotation, an experimental strategy was employed as described [ 64 ]. Briefly, FASTA sequences of the proteins were retrieved from the UniProt database [ 65 ], and PSORTb 3.0 [ 66 ], PSLpred [ 67 ], CELLO [ 68 ], and WolfPsort [ 69 ] servers were used to predict the subcellular localization of the molecules.…”

Section: Methodsmentioning

confidence: 99%

Small Myristoylated Protein-3, Identified as a Potential Virulence Factor in Leishmania amazonensis, Proves to be a Protective Antigen against Visceral Leishmaniasis

Pires-Oliveira

Martins

Santos

et al. 2018

IJMS

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In a proteomics approach conducted with Leishmania amazonensis, parasite proteins showed either an increase or a decrease in their expression content during extensive in vitro cultivation, and were related to the survival and the infectivity of the parasites, respectively. In the current study, a computational screening was performed to predict virulence factors among these molecules. Three proteins were selected, one of which presented no homology to human proteins. This candidate, namely small myristoylated protein-3 (SMP-3), was cloned, and its recombinant version (rSMP-3) was used to stimulate peripheral blood mononuclear cells (PBMCs) from healthy subjects living in an endemic area of leishmaniasis and from visceral leishmaniasis patients. Results showed high interferon-γ (IFN-γ) production and low levels of interleukin 10 (IL-10) in the cell supernatants. An in vivo experiment was then conducted on BALB/c mice, which were immunized with rSMP-3/saponin and later challenged with Leishmania infantum promastigotes. The rSMP-3/saponin combination induced high production of protein-specific IFN-γ, IL-12, and granulocyte-macrophage colony-stimulating factor (GM-CSF) by the spleen cells of the immunized mice. This pattern was associated with protection, which was characterized by a significant reduction in the parasite load in distinct organs of the animals. Altogether, these results have revealed that this new virulence factor is immunogenic in both mice and humans, and have proven its protective efficacy against visceral leishmaniasis in a murine model.

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An in silico functional annotation and screening of potential drug targets derived from Leishmania spp. hypothetical proteins identified by immunoproteomics

Cited by 17 publications

References 96 publications

UnderstandingLeishmaniaparasites through proteomics and implications for the clinic

UnderstandingLeishmaniaparasites through proteomics and implications for the clinic

Screening diagnostic candidates fromLeishmania infantumproteins for human visceral leishmaniasis using an immunoproteomics approach

Small Myristoylated Protein-3, Identified as a Potential Virulence Factor in Leishmania amazonensis, Proves to be a Protective Antigen against Visceral Leishmaniasis

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