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Proteomics Advances in the Study of Leishmania Parasites and Leishmaniasis

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Proteins and Proteomics of Leishmania and Trypanosoma

Part of the book series: Subcellular Biochemistry ((SCBI,volume 74))

Abstract

Leishmania spp. are digenetic parasites which cause a broad spectrum of fatal diseases in humans. These parasites, as well as the other trypanosomatid, regulate gene expression at the post-transcriptional and post-translational levels, so that a poor correlation is observed between mRNA content and translated proteins. The completion of the genomic sequencing of several Leishmania species has enormous relevance to the study of the leishmaniasis pathogenesis. The combination of the available genomic resources of these parasites with powerful high-throughput proteomic analysis has shed light on various aspects of Leishmania biology as well as on the mechanisms underlying the disease. Diverse proteomic approaches have been used to describe and catalogue global protein profiles of Leishmania spp., reveal changes in protein expression during development, determine the subcellular localization of gene products, evaluate host-parasite interactions and elucidate drug resistance mechanisms. The characterization of these proteins has advanced, although many fundamental questions remain unanswered. Here, we present a historic review summarizing the different proteomic technologies applied to the study of Leishmania parasites during the last decades and we discuss the proteomic discoveries that have contributed to the understanding of Leishmania parasites biology and leishmaniasis.

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Abbreviations

1DE:

One dimensional electrophoresis

2D-DIGE:

Two dimensional differential gel electrophoresis

2DE:

Two dimensional electrophoresis

2D-LC-MS/MS:

Two dimensional liquid chromatography coupled with tandem mass spectrometry

ATP:

Adenosine triphosphate

BLAST:

Basic local alignment search tool

DNA:

Deoxyribonucleic acid

EDTA:

Ethylenediamine tetra acetic acid

ESI:

Electrospray ionization

ESI-MS:

Electrospray ionization mass spectrometry

GFP:

Green fluorescent protein

GO:

Gene ontology

GP46:

Glycoprotein 46

GP63:

Glycoprotein 63 also called leishmanolysin and major surface peptidase

GTP:

Guanosine triphosphate

HSP60:

Heat shock protein 60

HSP70:

Heat shock protein 70

HSP90:

Heat shock protein 90

HSP100:

Heat shock protein 100

IEF:

Isoelectric focalization

IgG:

Immunoglobulin g

IgM:

Immunoglobulin m

iMAC:

Metal affinity chromatography

iTRAQ:

Isobaric tags for relative and absolute quantification

KMP-11:

Kinetoplastid membrane protein 11

LC-MS/MS:

Liquid chromatography coupled with tandem mass spectrometers

MALDI:

Matrix assisted laser desorption ionization

MALDI-MS:

Matrix assisted laser desorption ionization mass spectrometry

MALDI-MS/MS:

Matrix assisted laser desorption ionization tandem mass spectrometry

mRNA:

Messenger ribonucleic acid

MUDPIT:

Multidimensional protein identification

PTMs:

Post translational modifications

Rab7:

Ras-related protein 7

RNA:

Ribonucleic acid

SbIII:

Trivalent antimonials

SbV:

Pentavalent antimonials

SDS-PAGE:

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

SHERP:

Small hydrophilic endoplasmic reticulum-associated protein

SILAC:

Stable isotope labeling by amino acids in cell culture

SKRP:

Small-kinetoplastid-related-protein

TCA:

Trichloroacetic acid

Th1:

T helper 1

WHO:

World health organization

References

  • Abdo MG, Elamin WM, Khalil EA et al (2003) Antimony-resistant Leishmania donovani in eastern Sudan: incidence and in vitro correlation. East Mediterr Health 9:837–843

    CAS  Google Scholar 

  • Acestor N, Masina S, Walker J et al (2002) Establishing two-dimensional gels for the analysis of leishmania proteomes. Proteomics 7:877–879

    Google Scholar 

  • Adaui V, Castillo D, Zimic M et al (2011) Comparative gene expression analysis throughout the life cycle of Leishmania braziliensis: diversity of expression profiles among clinical isolates. PLoS Negl Trop Dis 5:e1021

    PubMed  CAS  Google Scholar 

  • Aebersold R, Mann M (2003) Mass spectrometry-based proteomics. Nature 422:198–207

    PubMed  CAS  Google Scholar 

  • Altschul SF, Gish W, Miller W et al (1990) Basic local alignment search tool. J Mol Biol 215:403–410

    PubMed  CAS  Google Scholar 

  • Alvar J, Vélez ID, Bern C et al (2012) Leishmaniasis worldwide and global estimates of its incidence. PLoS One 7:e35671

    PubMed  CAS  Google Scholar 

  • Babich H, Liebling EJ, Burger RF, Zuckerbraun HL, Schuck AG (2009) Choice of DMEM, formulated with or without pyruvate, plays an important role in assessing the in vitro cytotoxicity of oxidants and prooxidant nutraceuticals. In Vitro Cell Dev Biol Anim 45:226–233

    Google Scholar 

  • Bantscheff M, Schirle M, Sweetman G et al (2007) Quantitative mass spectrometry in proteomics: a critical review. Anal Bioanal Chem 389:1017–1031

    PubMed  CAS  Google Scholar 

  • Bendtsen JD, Jensen LJ, Blom N et al (2004a) Feature based prediction of non-classical and leaderless protein secretion. Protein Eng Des Sel 17:349–356

    PubMed  CAS  Google Scholar 

  • Bendtsen JD, Nielsen H, von Heijne G et al (2004b) Improved prediction of signal peptides: signal P 3.0. J Mol Biol 340:783–795

    PubMed  Google Scholar 

  • Bente M, Harder S, Wiesqiql M et al (2003) Developmentally induced changes of the proteome in the protozoan parasite Leishmania donovani. Proteomics 3:1811–1829

    PubMed  CAS  Google Scholar 

  • Berman JD, Chulay JD, Hendricks LD et al (1982) In vitro susceptibility of antimony resistant Leishmania to alternative drugs. J Infect Dis 145:279

    PubMed  CAS  Google Scholar 

  • Besteiro S, Williams RAM, Coombs GH et al (2007) Protein turnover and differentiation in leishmania. Int J Parasitol 37:1063–1075

    PubMed  CAS  Google Scholar 

  • Biyani N, Madhubala R (2012) Quantitative profiling of the promastigotes and the intracellular amastigotes of Leishmania donovani isolates identifies novel proteins having a role in Leishmania differentiation and intracellular survival. Bioch Biophys Acta 1824:1342–1350

    CAS  Google Scholar 

  • Biyani N, Singh AK, Mandal S et al (2011) Differential expression of proteins in antimony-susceptible and –resistant isolates of Leishmania donovani. Mol Biochem Parasitol 179:91–99

    PubMed  CAS  Google Scholar 

  • Bourdoiseau G, Hugnet C, Gonçalves RB et al (2009) Effective humoral and cellular immunoprotective response in LIESAp-MDP vaccinated protected dogs. Vet Immunol Immunopathol 128:71–78

    PubMed  CAS  Google Scholar 

  • Brobey RK, Mei FC, Cheng X et al (2006) Comparative two-dimensional electrophoresis maps of Leishmania amazonensis and Leishmania major braz. J Infect Dis 10:1–6

    Google Scholar 

  • Brotherton MA, Racine G, Ouanmeur AA et al (2012) Analysis of membrane-enriched and high molecular weight proteins in Leishmania infantum promastigotes and axenic amastigotes. J Proteome Res 11:3974–3985

    PubMed  CAS  Google Scholar 

  • Callahan HL, Portal AC, Devereaux R et al (1997) An axenic amastigote system for drug screening. Antimicrob Agents Chemother 41:818–822

    PubMed  CAS  Google Scholar 

  • Chawla B, Jhingram A, Panigrahi A et al (2011) Paromomycin affects translation and vesicle-mediated trafficking as revealed by proteomics of paromomycin–susceptible –resistant Leishmania donovani. PLoS One 6:e26660

    PubMed  CAS  Google Scholar 

  • Claros MG, Vincens P (1996) Computational method to predict mitochondrially imported proteins and their targeting sequences. Eur J Biochem 241:779–786

    PubMed  CAS  Google Scholar 

  • Clayton C (2002) Life without transcriptional control? From fly to man and back again. EMBO J 21:1881–1888

    PubMed  CAS  Google Scholar 

  • Coelho VTS, Oliveira JS, Valadares DG et al (2012) Identification of proteins in promastigote and amastigote-like Leishmania using an immunoproteomic approach. PLoS One 6:e1430

    CAS  Google Scholar 

  • Costa MM, Andrade HM, Bartholomeu DC et al (2011) Analysis of Leishmania chagasi by 2-D difference Gel electrophoresis (2-D DIGE) and immunoproteomic: identification of novel candidate antigens for diagnostic tests and vaccine. J Proteome Res 10:2172–2184

    PubMed  CAS  Google Scholar 

  • Croft SL, Sundar S, Fairlamb AH (2006) Drug resistance in leishmaniasis. Clin Microbiol Rev 19:111–126

    PubMed  CAS  Google Scholar 

  • Cuervo P, De Jesus JB (2012) Genetic expression and drug resistance, the role of proteomics. In: A. Ponte-Sucre et al. (eds.), Drug resistance in Leishmania parasites, DOI 10.1007/978-3-7091-1125-3_11, Springer-Verlag, Wien

  • Cuervo P, De Jesus JB, Junqueira M et al (2007) Proteome analysis of Leishmania (Viannia) braziliensis by two-dimensional gel electrophoresis and mass spectrometry. Mol Biochem Parasitol 154:6–21

    PubMed  CAS  Google Scholar 

  • Cuervo P, De Jesus JB, Saboia-Vahia L et al (2009) Proteomic characterization of the released/secreted proteins of Leishmania (Viannia) braziliensis promastigotes. Proteomics 73:79–92

    PubMed  CAS  Google Scholar 

  • Cuervo P, Domon GB, De Jesus JB (2010) Proteomics of trypanosomatids of human medical importance. J Proteomics 73:845–867

    PubMed  CAS  Google Scholar 

  • Cunningham ML, Zvelebil MJ, Fairlamb AH (1994) Mechanism of inhibition of trypanothione reductase and glutathione reductase by trivalent organic arsenicals. Eur J Biochem 221:285–295

    PubMed  CAS  Google Scholar 

  • da Silva VO, Borja-Cabrera GP, Correia Pontes NN et al (2001) A phase III trial of efficacy of the FML-vaccine against canine kalazar in an endemic area of brazil (São gonçalo do amarante, RN). Vaccine 19:1068–1081

    Google Scholar 

  • Davis BD (1987) Mechanism of bactericidal action of aminoglycosides. Microbiol Rev 51:341–350

    PubMed  CAS  Google Scholar 

  • De Oliveira AHC, Ruiz JC, Cruz AK et al (2006) Subproteomic analysis of soluble proteins of the microsomal fraction from two Leishmania species. Comp Biochem Physiol 1:300–308

    Google Scholar 

  • Dea-Ayuela MA, Rama-Iñiguez S, Bólas-Fernandéz F (2006) Proteomic analysis of antigens from Leishmania infantum promastigotes. Proteomics 6:4187–4194

    PubMed  CAS  Google Scholar 

  • Deplege DP, Evans KJ, Ivens AC et al (2009) Comparative expression profiling of Leishmania: modulation in gene expression between species and in different host genetic backgrounds. PLoS Negl Trop Dis 3:e476

    Google Scholar 

  • Domon B, Aebersold R (2006) Mass spectrometry and protein analysis. Science 312:212–217

    PubMed  CAS  Google Scholar 

  • El Fadili K, Drummelsmith J, Gaétan R et al (2009) Down regulation of KMP-11 in Leishmania infantum axenic antimony resistant amastigotes as revealed by a proteomic screen. Exp Parasitol 123:51–57

    PubMed  Google Scholar 

  • El Fakhry Y, Oullette M, Papadopoulou B (2002) A proteomic approach to identify developmentally regulated proteins in Leishmania infantum. Proteomics 2:1007–1017

    PubMed  Google Scholar 

  • Ephros M, Bitnun A, Shaked P et al (1999) Stage-specific activity of pentavalent antimony against Leishmania donovani axenic amastigotes. Antimicrob Agents Chemother 43:278–282

    PubMed  CAS  Google Scholar 

  • Faraut-Gambarelli F, Piarroux R, Deniau M et al (1997) In vitro and in vivo resistance of Leishmania infantum to meglumine antimoniate: a study of 37 strains collected from patients with visceral leishmaniasis. Antimicrob Agents Chemother 41:827–830

    PubMed  CAS  Google Scholar 

  • Fasel N, Acestor N, Fadili-Kündig, et al. (2008) The Leishmania proteome. In: Myler PJ and Fasel N (eds) (Caister Academic Press) Leishmania after genome. Norfolk

    Google Scholar 

  • Fenn J, Mann M, Meng CK et al (1989) Electrospray ionization for mass spectrometry of large biomolecules. Science 246:64–71

    PubMed  CAS  Google Scholar 

  • Fernandes AP, Costa MM, Coelho EA et al (2008) Protective immunity against challenge with Leishmania (Leishmania) chagasi in beagle dogs vaccinated with recombinant A2 protein. Vaccine 26:5888–5895

    PubMed  CAS  Google Scholar 

  • Forgber M, Basu R, Roychoudhury K et al (2006) Mapping the antigenicity of the parasites in Leishmania donovani infection by proteome serology. PLoS One 1:e40

    PubMed  Google Scholar 

  • Foucher AL, Papadopoulou B, Ouellette M (2006) Prefractionation by digitonin extraction increases representation of the cytosolic and intracellular proteome of Leishmania infantum. J Proteome Res 5:1741–1750

    PubMed  CAS  Google Scholar 

  • Franke ED, McGreevy PB, Katz SP et al (1985) Growth cycle dependent generation of complement-resistant Leishmania promastigotes. J Immunol 134:2713–2718

    PubMed  CAS  Google Scholar 

  • Fuertes MA, Berberich C, Lozano RM et al (1999) Folding stability of the kinetoplastid membrane protein-11 (KMP-11) from Leishmania infantum. Eur J Biochem 260:559–567

    PubMed  CAS  Google Scholar 

  • Garg R, Gupta SK, Tripathi P et al (2006) Leishmania donovani: identification of stimulatory soluble proteins using cured human and hamster lymphocytes for their prophylactic potential against visceral leishmaniasis. Vaccine 24:2900–2909

    PubMed  CAS  Google Scholar 

  • Góngorra R, Acestor N, Quadroni M et al (2003) Mapping the proteome of Leishmania Viannia parasites using two-dimensional electrophoresis polyacrilamide gel electrophoresis and associated technologies. Biomedica 23:153–160

    Google Scholar 

  • Görg A, Drews O, Lück C et al (2009) 2-DE with IPGs. Electrophoresis 30:122–132

    Google Scholar 

  • Gourbal B, Sonuc N, Bhattacharjee H et al (2004) Drug uptake and modulation of drug resistance in Leishmania by an aquaglyceroporin. J Biol Chem 279:31010–31017

    PubMed  CAS  Google Scholar 

  • Gupta SK, Sisodia BS, Sinha S et al (2007) Proteomic approach for identification and characterization of novel immunostimulatory proteins from soluble antigens of Leishmania donovani promastigotes. Proteomics 7:816–823

    PubMed  CAS  Google Scholar 

  • Gygi SP, Corthals GL, Zhang Y et al (2000) Evaluation of two-dimensional gel electrophoresis-based proteome analysis technology. Proc Natl Acad Sci USA 97:9390–9395

    PubMed  CAS  Google Scholar 

  • Haile S, Papadopoulou B (2007) Developmental regulation of gene expression in trypanosomatid parasitic protozoa. Curr Opin Microbiol 10:569–577

    PubMed  CAS  Google Scholar 

  • Handman E, Mitchell GF, Goding JW (1981) Identification and characterization of protein antigens of Leishmania tropica isolates. J Immunol 126:508–512

    PubMed  CAS  Google Scholar 

  • Hem S, Gherardini PF, Osorio Y, Fortéa J et al (2010) Identification of Leishmania-specific protein phosphorylations sites by LC-ESI-MS/MS and comparative genomic analyses. Proteomics 10:3868–3883

    PubMed  CAS  Google Scholar 

  • Holzer TR, McMaster WR, Forney JD (2006) Expression profiling by whole-genome interspecies microarray hybridization reveals differential gene expression in procyclic promastigotes, lesion-derived amastigotes, and axenic amastigotes in Leishmania Mexicana. Mol Biochem Parasitol 146:198–218

    PubMed  CAS  Google Scholar 

  • Ivens AC, Peacock CS, Worthey EA et al (2005) The genome of the kinetoplastid parasite, Leishmania major. Science 309:436–442

    PubMed  Google Scholar 

  • Jardim A, Funk V, Caprioli RM et al (1995) Isolation and structural characterization of Leishmania donovani kinetoplastid membrane protein 11, a major immunoreactive membrane glycoprotein. Biochem J 305:307–313

    PubMed  CAS  Google Scholar 

  • Karas M, Hilenkamp F (1988) Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons. Anal Chem 15:2299–2301

    Google Scholar 

  • Knuepfer E, Stierhof Y, McKean PG et al (2001) Characterization of a differentially expressed protein that shows an unusual localization to intracellular membranes in Leishmania major. Biochem J 356:335–344

    PubMed  CAS  Google Scholar 

  • Laemli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    Google Scholar 

  • Leifso K, Cohen-Freue G, Dogra N et al (2007) Genomic and proteomic expression analysis of Leishmania promastigote and amastigote life stages: the Leishmania genome is constitutively expressed. Mol Biochem Parasitol 152:35–46

    PubMed  CAS  Google Scholar 

  • Lemesre JL, Holzmuller P, Cavaleyra M et al (2005) Protection against experimental visceral leishmaniasis infection in dogs immunized with purified excreted secretes antigen of Leishmania infantum promastigotes. Vaccine 23:2825–2840

    PubMed  CAS  Google Scholar 

  • Lemesre JL, Holzmuller P, Gonçalves RB et al (2007) Long lasting protection against canine visceral leishmaniasis using the LIESAp-MDP vaccine in endemic areas of France: double blind randomized efficacy field trial. Vaccine 25:4223–4234

    PubMed  CAS  Google Scholar 

  • Lira R, Sundar S, Makharia A et al (1999) Evidence that the high incidence of treatment failures in Indian kala-azar is due to the emergence of antimony-resistant strains of Leishmania donovani. J Infect Dis 180:564–567

    PubMed  CAS  Google Scholar 

  • Matsuidara (1987) Sequence from picomole quantities of proteins electroblotted onto polyvinylidene difluoride membranes. J Biol Chem 262:10035–10038

    Google Scholar 

  • McNicoll F, Drummelsmith J, Müller M et al (2006) A combined proteomic and transcriptomic approach to the study of stage differentiation in leishmania infantum. Proteomics 6:3567–3581

    PubMed  CAS  Google Scholar 

  • Mojtahedi Z, Clos J, Kamali-Sarvestani E (2008) Leishmania major: identification of developmentally regulated proteins in procyclic and metacyclic promastigotes. Exp Parasitol 119:422–429

    PubMed  CAS  Google Scholar 

  • Morales MA, Watanabe R, Laurent C et al (2008) Phosphoproteomic analysis of Leishmania donovani pro- and amastigote stages. Proteomics 8:350–363

    PubMed  CAS  Google Scholar 

  • Morales MA, Watanabe R, Dacher M et al (2010) Phosphoproteome dynamics reveal heat-shock protein complexes specific to the Leishmania donovani infectious stage. Proc Natl Acad Sci USA 107:8381–8386

    PubMed  CAS  Google Scholar 

  • Mottram JC, Frame MJ, Brooks DR et al (1997) The multiple cpb cysteine proteinase genes of Leishmania Mexicana encode isoenzymes that differ in their stage. J Biol Chem 272:14285–14293

    PubMed  CAS  Google Scholar 

  • Murray HW, Berman JD, Davies CR et al (2005) Advances in leishmaniasis. Lancet 366:1561–1577

    PubMed  CAS  Google Scholar 

  • Nugent PG, Karsani SA, Wait R et al (2004) Proteomic analysis of Leishmania mexicana differentiation. Mol Biochem Parasitol 136:51–62

    PubMed  CAS  Google Scholar 

  • O’Farrel PH (1975) High resolution two-dimensional electrophoresis of proteins. J Biol Chem 250:4007–4021

    Google Scholar 

  • Paape D, Aebischer T (2011) Contribution of proteomics of Leishmania spp. To the understanding of differentiation, drug resistance mechanisms, vaccine and drug development. J Proteomics 74:1614–1624

    PubMed  CAS  Google Scholar 

  • Paape D, Lippuner C, Schmid M et al (2008) Transgenic, fluorescent Leishmania mexicana allow direct analysis of the proteome of intracellular amastigotes. Mol Cell Proteomics 7:1688–1701

    PubMed  CAS  Google Scholar 

  • Paape D, Barrios-Llerena ME, Le Bihan T et al (2010) Gel free analysis of intracellular Leishmania Mexicana. Mol Biochem Parasitol 169:108–114

    PubMed  CAS  Google Scholar 

  • Palacios R, Osorio LE, Grajalew LF et al (2001) Treatment failure in children in a randomized clinical trial with 10 and 20 days of meglumine antimonate for cutaneous leishmaniasis due to Leishmania Viannia species. Am J Trop Med Hyg 64:187–193

    PubMed  CAS  Google Scholar 

  • Peacock CS, Seeger K, Harris D et al (2007) Comparative genomic analysis of three Leishmania species that cause diverse human disease. Nat Genet 39:839–847

    PubMed  CAS  Google Scholar 

  • Pescher P, Blisnick T, Bastin P et al (2011) Quantitative proteome profiling informs on phenotypic traits that adapt Leishmania donovani for axenic and intracellular proliferation. Cell Microbiol 13:978–991

    PubMed  CAS  Google Scholar 

  • Petrak J, Ivanek R, Toman O et al (2008) Déjà vu in proteomics. A hit parade of repeatedly identified differentially expressed proteins. Proteomics 8:1744–1749

    PubMed  CAS  Google Scholar 

  • Reithinger R, Dujardin JC, Louzir H et al (2007) Cutaneous leishmaniasis. Lancet 7:581–596

    Google Scholar 

  • Rochette A, Raymond F, Ubeda J et al (2008) Genome-wide gene expression profiling analysis of Leishmania major and Leishmania infantum developmental stages reveals substantial differences between the two species. BMC Genomics 29:255

    Google Scholar 

  • Rogers MB, Hilley JD, Dickens NJ et al (2011) Chromosome and gene copy number variation allow major structural change between species and strains of Leishmania. Gener Res 21:2129–2142

    CAS  Google Scholar 

  • Rojas R, Valderrama L, Valderrama M et al (2006) Resistance to antimony and treatment failure in human Leishmania (Viannia) infection. J Infect Dis 193:1375–1383

    PubMed  CAS  Google Scholar 

  • Rosenzweig D, Smith D, Opperdoes F et al (2008a) Retooling Leishmania metabolism: from sand fly gut to human macrophage. FASEB J 22:590–602

    PubMed  CAS  Google Scholar 

  • Rosenzweig D, Smith D, Myler P et al (2008b) Post-translational modifications of cellular proteins during Leishmania donovani differentiation. Proteomics 8:1843–1850

    PubMed  CAS  Google Scholar 

  • Sacks DL, Perkins PV (1984) Identification of an infective stage of Leishmania promastigotes. Science 223:1417–1419

    PubMed  CAS  Google Scholar 

  • Santos FN, Borja-Cabrera GP, Miyashiro LM et al (2007) Immunotherapy against experimental canine visceral leishmaniasis with the saponin enriched leishimune vaccine. Vaccine 25:6176–6190

    PubMed  CAS  Google Scholar 

  • Saravia NG, Gemmel MA, Nance SL et al (1984) Two-dimensional electrophoresis used to differentiate the causal agents of American tegumentary leishmaniasis. Clin Chem 30:2048–2052

    PubMed  CAS  Google Scholar 

  • Sereno D, Holzmuller P, Mangot I et al (2001) Antimonial-mediated DNA fragmentation in Leishmania infantum amastigotes. Antimicrob Agents Chemother 45:2064–2069

    PubMed  CAS  Google Scholar 

  • Shaked-Mishan P, Ulrich N, Ephros M et al (2001) Novel intracellular SbV reducing activity correlates with antimony susceptibility in Leishmania donovani. J Biol Chem 276:3971–3976

    PubMed  CAS  Google Scholar 

  • Silverman JM, Chan SK, Robinson DP et al (2008) Proteomic analysis of the secretome of Leishmania donovani. Genome Biol 9:R35

    PubMed  Google Scholar 

  • Silverman JM, Clos J, de Oliveira CC et al (2010a) an exosome-based secretion pathway is responsible for protein export from Leishmania and communication with macrophages. J Cell Sci 123:842–852

    PubMed  CAS  Google Scholar 

  • Silverman JM, Clos J, Horakova E et al (2010b) Leishmania exosomes modulate innate and adaptative immune responses through effects on monocyte and dendritic cells. J Immuno 185:5011–5022

    CAS  Google Scholar 

  • Sudhandiran G, Shaha C (2003) Antimonial-induced increase in intracellular Ca2+ through non selective cation channels in the host and the parasite is responsible for apoptosis in intracellular Leishmania donovani amastigotes. J Biol Chem 278:25120–25132

    PubMed  CAS  Google Scholar 

  • Tanaka K, Ido K, Akita S et al (1988) Protein and polymer analyses up to m/z 100000 by laser ionization time of flight mass spectrometry. Rapid Commun Mass Spectrom 2:151–153

    CAS  Google Scholar 

  • Vergnes B, Gourbal B, Girard I et al (2007) A proteomics screen implicates HSP83 and a small kinetoplastid calpain-related protein in drug resistance in Leishmania donovani clinical field isolates by modulating drug-induced programmed cell death. Mol Cell Proteomics 6:88–101

    PubMed  CAS  Google Scholar 

  • Walker J, Vasquez JJ, Gomez MA et al (2006) Identification of developmentally-regulated proteins in Leishmania panamensis by proteome profiling of promastigotes and axenic amastigotes. Mol Biochem Parasitol 147:64–73

    PubMed  CAS  Google Scholar 

  • Walker J, Gongorra R, Vasquez JJ et al (2012) Discovery of factors linked to antimony resistance in Leishmania panamensis through differential proteome analysis. Mol Biochem Parasitol 183:166–176

    PubMed  CAS  Google Scholar 

  • Wang X, Perez E, Liu R, Yan LJ, Mallet RT, Yang SH (2007) Pyruvate protects mitochondria from oxidative stress in human neuroblastoma SK-N-SH cells. Brain Res 1132:1–9

    PubMed  CAS  Google Scholar 

  • Wastling JM, Armstrong SD, Krishna R et al (2012) Parasites, proteomes and systems: has Descartes’ clock run out of time? Parasitology 139:1103–1118

    PubMed  CAS  Google Scholar 

  • WHO (2010) Control of Leishmaniasis. WHO Technical Report Series 949. Geneva

    Google Scholar 

  • Wyllie S, Cunningham ML, Fairlamb AH (2004) Dual action of antimonial drugs on thiol redox metabolism in the human pathogen Leishmania donovani. J Biol Chem 279:39925–39932

    PubMed  CAS  Google Scholar 

  • Yao C, Li Y, Donelson JE et al (2010) Proteomic examination of Leishmania chagasi plasma membrane proteins: contrast between avirulent and virulent (metacyclic) parasite forms. Proteomics Clin Appl 4:4–16

    PubMed  CAS  Google Scholar 

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de Jesus, J.B., Mesquita-Rodrigues, C., Cuervo, P. (2014). Proteomics Advances in the Study of Leishmania Parasites and Leishmaniasis. In: Santos, A., Branquinha, M., d’Avila-Levy, C., Kneipp, L., Sodré, C. (eds) Proteins and Proteomics of Leishmania and Trypanosoma. Subcellular Biochemistry, vol 74. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7305-9_14

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