Hostname: page-component-8448b6f56d-m8qmq Total loading time: 0 Render date: 2024-04-24T13:54:29.307Z Has data issue: false hasContentIssue false
  • English
  • Français

An immunoproteomics approach to identify Leishmania infantum proteins to be applied for the diagnosis of visceral leishmaniasis and human immunodeficiency virus co-infection

Published online by Cambridge University Press:  20 April 2020

Amanda S. Machado ,
Fernanda F. Ramos ,
João A. Oliveira-da-Silva ,
Thaís T. O. Santos ,
Grasiele S. V. Tavares ,
Lourena E. Costa ,
Daniela P. Lage ,
André Teixeira-Ferreira ,
Jonas Perales  and
Ana Paula Fernandes
...Show all authors
Amanda S. Machado
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Fernanda F. Ramos
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
João A. Oliveira-da-Silva
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Thaís T. O. Santos
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Grasiele S. V. Tavares
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Lourena E. Costa
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Daniela P. Lage
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
André Teixeira-Ferreira
Affiliation:
Departamento de Fisiologia e Farmacodinâmica, Laboratório de Toxicologia, FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil
Jonas Perales
Affiliation:
Departamento de Fisiologia e Farmacodinâmica, Laboratório de Toxicologia, FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil
Ana Paula Fernandes
Affiliation:
Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Ricardo L. F. Moreira
Affiliation:
Hospital Eduardo de Menezes, FHEMIG, Belo Horizonte, Minas Gerais, Brazil
Mariana C. Duarte
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Unaí Tupinambás
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Rachel B. Caligiorne
Affiliation:
Instituto de Ensino e Pesquisa, Santa Casa de Belo Horizonte, Belo Horizonte, Minas Gerais, Brazil
Gláucia F. Cota
Affiliation:
Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil
Eduardo A. F. Coelho*
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Fernanda Ludolf
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
*
Author for correspondence: Eduardo A.F. Coelho, E-mail: eduardoferrazcoelho@yahoo.com.br
Get access Rights & Permissions [Opens in a new window]

Abstract

The co-infection between visceral leishmaniasis (VL) and human immunodeficiency virus (HIV) has increased in several countries in the world. The current serological tests are not suitable since they present low sensitivity to detect the most of VL/HIV cases, and a more precise diagnosis should be performed. In this context, in the present study, an immunoproteomics approach was performed using Leishmania infantum antigenic extracts and VL, HIV and VL/HIV patients sera, besides healthy subjects samples; aiming to identify antigenic markers for these clinical conditions. Results showed that 43 spots were recognized by antibodies in VL and VL/HIV sera, and 26 proteins were identified by mass spectrometry. Between them, β-tubulin was expressed, purified and tested in ELISA experiments as a proof of concept for validation of our immunoproteomics findings and results showed high sensitivity and specificity values to detect VL and VL/HIV patients. In conclusion, the identified proteins in the present work could be considered as candidates for future studies aiming to improvement of the diagnosis of VL and VL/HIV co-infection.

Keywords

Diagnosishuman immunodeficiency virusimmunoproteomicsrecombinant proteinsvisceral leishmaniasisVL/HIV co-infection
Type
Research Article
Information
Parasitology , Volume 147 , Issue 9 , August 2020 , pp. 932 - 939
Check for updates
Copyright
Copyright © The Author(s) 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alvar, J, Aparicio, P, Aseffa, A, Den Boer, M, Canavate, C, Dedet, JP, Gradoni, L, Ter Horst, R, Lopez-Velez, R and Moreno, J (2008) The relationship between leishmaniasis and AIDS: the second 10 years. Clinical Microbiology Reviews 21, 334–359.CrossRefGoogle ScholarPubMed
Avishek, K, Ahuja, K, Pradhan, D, Gannavaram, S, Selvapandiyan, A, Nakhasi, HL and Salotra, P (2018) A Leishmania-specific gene upregulated at the amastigote stage is crucial for parasite survival. Parasitology Research 117, 3215–3228.CrossRefGoogle ScholarPubMed
Bradford, MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry 72, 248–254.CrossRefGoogle ScholarPubMed
Charest, H and Matlashewski, G (1994) Developmental gene expression in Leishmania Donovani: differential cloning and analysis of an amastigote-stage-specific gene. Molecular and Cellular Biology 14, 2975–2984.CrossRefGoogle ScholarPubMed
Chiranjivi, AK and Dubey, VK (2018) Dihydrolipoamide dehydrogenase from Leishmania Donovani: new insights through biochemical characterization. International Journal of Biological Macromolecules 112, 1241–1247.CrossRefGoogle ScholarPubMed
Coelho, EA, Tavares, CA, Carvalho, FA, Chaves, KF, Teixeira, KN, Rodrigues, RC, Charest, H, Matlashewski, G, Gazzinelli, RT and Fernandes, AP (2003) Immune responses induced by the Leishmania (Leishmania) donovani A2 antigen, but not by the LACK antigen, are protective against experimental Leishmania (Leishmania) amazonensis Infection. Infection and Immunity 71, 3988–3994.CrossRefGoogle Scholar
Coelho, VT, Oliveira, JS, Valadares, DG, Chávez-Fumagalli, MA, Duarte, MC, Lage, PS, Soto, M, Santoro, MM, Tavares, CA, Fernandes, AP and Coelho, EA (2012) Identification of proteins in promastigote and amastigote-like Leishmania Using an immunoproteomic approach. PLoS Neglected Tropical Diseases 6, e1430.CrossRefGoogle ScholarPubMed
Corpet, F (1988) Multiple sequence alignment with hierarchical clustering. Nucleic Acids Research 16, 10881–10890.CrossRefGoogle ScholarPubMed
Costa, LE, Alves, PT, Carneiro, AP, Dias, ACS, Fujimura, PT, Araujo, GR, Tavares, GSV, Ramos, FF, Duarte, MC, Menezes-Souza, D, Briza, P, Briza, FF, Coelho, EAF and Goulart, LR (2019) Leishmania Infantum β-tubulin identified by reverse engineering technology through phage display applied as theranostic marker for human visceral leishmaniasis. International Journal Of Molecular Sciences 20, 1812.CrossRefGoogle ScholarPubMed
Cota, GF, Sousa, MR and Rabello, A (2011) Predictors of visceral leishmaniasis relapse in HIV-infected patients: a systematic review. PLoS Neglected Tropical Diseases 5, e1153.CrossRefGoogle ScholarPubMed
Cota, GF, Sousa, MR, Demarqui, FN and Rabello, A (2012) The diagnostic accuracy of serologic and molecular methods for detecting visceral leishmaniasis in HIV infected patients: meta-analysis. PLoS Neglected Tropical Diseases 6, e1665.CrossRefGoogle ScholarPubMed
Cota, GF, Sousa, MR, Freitas-Nogueira, BM, Gomes, LI, Oliveira, E, Assis, TS, Mendonça, AL, Pinto, BF, Saliba, JW and Rabello, A (2013) Comparison of parasitological, serological, and molecular tests for visceral leishmaniasis in HIV-infected patients: a cross-sectional delayed-type study. The American Journal of Tropical Medicine and Hygiene 89, 570–577.CrossRefGoogle ScholarPubMed
Dey, R, Meneses, C, Salotra, P, Kamhawi, S, Nakhasi, HL and Duncan, R (2010) Characterization of a Leishmania stage-specific mitochondrial membrane protein that enhances the activity of cytochrome c oxidase and its role in virulence. Molecular Microbiology 77, 399–414.CrossRefGoogle ScholarPubMed
Dhom-Lemos, L, Viana, AG, Cunha, JLR, Cardoso, MS, Mendes, TAO, Pinheiro, GRG, Siqueira, WF, Lobo, FP, Teles, LF, Bueno, LL, Guimarães-Carvalho, SF, Bartholomeu, DC and Fujiwara, RT (2019) Leishmania Infantum recombinant kinesin degenerated derived repeat (rKDDR): a novel potential antigen for serodiagnosis of visceral leishmaniasis. PLoS One 14, e0211719.CrossRefGoogle ScholarPubMed
Duarte, MC, Pimenta, DC, Menezes-Souza, D, Magalhães, RD, Diniz, JL, Costa, LE, Chávez-Fumagalli, MA, Lage, PS, Bartholomeu, DC, Alves, MJ, Fernandes, AP, Soto, M, Tavares, CA, Gonçalves, DU, Rocha, MO and Coelho, EA (2015) Proteins selected in Leishmania (Viannia) braziliensis By an immunoproteomic approach with potential serodiagnosis applications for tegumentary leishmaniasis. Clinical and Vaccine Immunology 22, 1187–1196.CrossRefGoogle ScholarPubMed
Hot, A, Schmulewitz, L, Viard, JP and Lortholary, O (2007) Fever of unknown origin in HIV/AIDS patients. Infectious Disease Clinics of North America 21, 1013–1032.CrossRefGoogle ScholarPubMed
Humbert, MV, Costa, LE, Katis, I, Ramos, FF, Machado, AS, Sones, C, Coelho, EAF and Christodoulides, M (2019) A rapid diagnostic test for human visceral leishmaniasis using novel Leishmania Antigens in a laser direct-write lateral flow device. Emerging Microbes & Infections 8, 1178–1185.CrossRefGoogle Scholar
Kaur, J and Kaur, S (2013) ELISA And western blotting for the detection of Hsp70 and Hsp83 antigens of Leishmania donovani. Journal of Parasitic Diseases 37, 68–73.Google ScholarPubMed
Kelleher, M, Curtis, JM, Sacks, DL, Handman, E and Bacic, A (1994) Epitope mapping of monoclonal antibodies directed against lipophosphoglycan of Leishmania major Promastigotes. Molecular Biochemistry and Parasitology 66, 187–200.CrossRefGoogle ScholarPubMed
Kumar, P, Pai, K, Tripathi, K, Pandey, HP and Sundar, S (2002) Immunoblot analysis of the humoral immune response to Leishmania Donovani polypeptides in cases of human visceral leishmaniasis: its usefulness in prognosis. Clinical and Diagnostic Laboratory Immunology 9, 1119–1123.Google ScholarPubMed
Lage, DP, Ludolf, F, Silveira, PC, Machado, AS, Ramos, FF, Dias, DS, Ribeiro, PAF, Costa, LE, Vale, DL, Tavares, GSV, Martins, VT, Chávez-Fumagalli, MA, Caligiorne, RB, Chaves, AT, Gonçalves, DU, Rocha, MOC, Duarte, MC and Coelho, EAF (2019) Screening diagnostic candidates from Leishmania Infantum proteins for human visceral leishmaniasis using an immunoproteomics approach. Parasitology 146, 1467–1476.CrossRefGoogle ScholarPubMed
Lima, MP, Costa, LE, Lage, DP, Dias, DS, Ribeiro, PAF, Machado, AS, Ramos, FF, Salles, BCS, Fagundes, MI, Carvalho, GB, Franklin, ML, Chávez-Fumagalli, MA, Machado-de-Ávila, RA, Menezes-Souza, D, Duarte, MC, Teixeira, AL, Gonçalves, DU and Coelho, EAF (2018) Diagnostic application of recombinant Leishmania Proteins and evaluation of their in Vitro Immunogenicity after stimulation of immune cells collected from tegumentary leishmaniasis patients and healthy individuals. Cellular Immunology 334, 61–69.CrossRefGoogle ScholarPubMed
Lindoso, JAL, Moreira, CHV, Cunha, MA and Queiroz, IT (2018) Visceral Leishmaniasis and HIV co-infection: current perspectives. HIV AIDS (Auckland. N.Z) 10, 193–201.Google ScholarPubMed
Maharana, BR, Tewari, AK and Veer, S (2015) An overview on kinetoplastid paraflagellar rod. Journal of Parasitic Diseases 39, 589–595.CrossRefGoogle ScholarPubMed
Martins, VT, Duarte, MC, Lage, DP, Costa, LE, Carvalho, AM, Mendes, TA, Roatt, BM, Menezes-Souza, D, Soto, M and Coelho, EA (2017) A recombinant chimeric protein composed of human and mice-specific CD4 and CD8 T-cell epitopes protects against visceral leishmaniasis. Parasite Immunology 39(1). doi: 10.1111/pim.12359CrossRefGoogle ScholarPubMed
McKean, PG, Denny, PW, Knuepfer, E, Keen, JK and Smith, DF (2001) Phenotypic changes associated with deletion and overexpression of a stage-regulated gene family in Leishmania. Cellular Microbiology 3, 511–523.CrossRefGoogle ScholarPubMed
Menezes-Souza, D, Mendes, TA, Gomes, MS, Reis-Cunha, JL, Nagem, RA, Carneiro, CM, Coelho, EA, Galvão, LM, Fujiwara, RT and Bartholomeu, DC (2014) Epitope mapping of the HSP83.1 protein of Leishmania braziliensis discloses novel targets for immunodiagnosis of tegumentary and visceral clinical forms of leishmaniasis. Clinical and Vaccine Immunology 21, 949–959.CrossRefGoogle ScholarPubMed
Petitdidier, E, Pagniez, J, Pissarra, J, Holzmuller, P, Papierok, G, Vincendeau, P, Lemesre, JL and Bras-Gonçalves, R (2019) Peptide-based vaccine successfully induces protective immunity against canine visceral leishmaniasis. NPJ Vaccines 4, 49.CrossRefGoogle ScholarPubMed
Russo, R, Laguna, F, Lopez-Velez, R, Medrano, FJ, Rosenthal, E, Cacopardo, B and Nigro, L (2003) Visceral leishmaniasis in those infected with HIV: clinical aspects and other opportunistic infections. Annals of Tropical Medicine and Parasitology 97, 99–105.CrossRefGoogle ScholarPubMed
Santos-Gomes, G, Gomes-Pereira, S, Campino, L, Araújo, MD and Abranches, P (2000) Performance of immunoblotting in diagnosis of visceral leishmaniasis in human immunodeficiency virus-Leishmania sp.-co-infected patients. Journal of Clinical Microbiology 38, 175–178.Google ScholarPubMed
Santos, TTO, Cardoso, MS, Machado, AS, Siqueira, WF, Ramos, FF, Oliveira-da-Silva, JA, Tavares, GSV, Lage, DP, Costa, LE, Freitas, CS, Martins, VT, Bandeira, RS, Chávez-Fumagalli, MA, Lyon, S, Moreira, RLF, Magalhães-Soares, Df, Silveira, JAG, Tupinambás, U, Caligiorne, RB, Chaves, AT, Rocha, MOC, Fujiwara, RT and Coelho, EAF (2019) Recombinant Leishmania Eukaryotic elongation factor-1 beta protein: a potential diagnostic antigen to detect tegumentary and visceral leishmaniasis in dogs and humans. Microbial Pathogenesis 137, 103783.CrossRefGoogle ScholarPubMed
Silva, MRB, Brandão, NAA, Colovati, M, Sousa, MMP, Lima, LC, Dorta, ML, Ribeiro-Dias, F, Costa, DL, Costa, CHN and Oliveira, MAP (2018) Performance of two immunochromatographic tests for diagnosis of visceral leishmaniasis in patients co-infected with HIV. Parasitology Research 117, 419.CrossRefGoogle Scholar
Sivakumar, R, Sharma, P, Chang, KP and Singh, S (2006) Cloning, expression, and purification of a novel recombinant antigen from Leishmania donovani. Protein Expression and Purification 46, 156–165.CrossRefGoogle ScholarPubMed
Srivastava, P, Dayama, A, Mehrotra, S and Sundar, S (2011) Diagnosis of visceral leishmaniasis. Royal Society of Tropical Medicine and Hygiene 105, 1–6.CrossRefGoogle ScholarPubMed
Srividya, G, Kulshrestha, A, Singh, R and Salotra, P (2012) Diagnosis of visceral leishmaniasis: developments over the last decade. Parasitology Research 110, 1065.CrossRefGoogle ScholarPubMed
Torres-Guerrero, E, Quintanilla-Cedillo, MR, Ruiz-Esmenjaud, J and Arenas, R (2017) Leishmaniasis: a review. F1000 Research 6, 750.CrossRefGoogle ScholarPubMed
Vale, DL, Dias, DS, Machado, AS, Ribeiro, PAF, Lage, DP, Costa, LE, Steiner, BT, Tavares, GSV, Ramos, FF, Martínez-Rodrigo, A, Chávez-Fumagalli, MA, Caligiorne, RB, Magalhães-Soares, DF, Silveira, JAG, Machado-de-Ávila, RA, Teixeira, AL and Coelho, EAF (2019) Diagnostic evaluation of the amastin protein from Leishmania Infantum in canine and human visceral leishmaniasis and immunogenicity in human cells derived from patients and healthy controls. Diagnostic Microbiology and Infectious Diseases 95, 134–143.CrossRefGoogle ScholarPubMed
Vasconcelos, EJ, Terrão, MC, Ruiz, JC, Vêncio, RZ and Cruz, AK (2012) In silico Identification of conserved intercoding sequences in Leishmania Genomes: unraveling putative cis-regulatory elements. Molecular Biochemistry and Parasitology 183, 140–150.CrossRefGoogle ScholarPubMed
World Health Organization (2012) UNAIDS Report on the Global AIDS Epidemic. Global Report, Geneva, Switzerland: World Health Organization.Google Scholar
World Health Organization (2019) Leishmaniasis and HIV coinfection. Retrieved from the World Health Organization website: https://www.who.int/news-room/fact-sheets/detail/hiv-aids (Accessed 18 October 2019).Google Scholar
Yang, X and Borchardt, RT (2000) Overexpression, purification, and characterization of S-adenosyl homocysteine hydrolase from Leishmania donovani. Archives of Biochemistry and Biophysics 15, 272–280.CrossRefGoogle Scholar