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BioMed Research International
Volume 2015, Article ID 301326, 21 pages
http://dx.doi.org/10.1155/2015/301326
Review Article

Molecular Chaperones of Leishmania: Central Players in Many Stress-Related and -Unrelated Physiological Processes

1Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Universidad Autónoma de Madrid, 28049 Madrid, Spain
2Departamento de Parasitología, Instituto de Medicina Tropical “Pedro Kourí”, 17100 Habana, Cuba

Received 7 March 2015; Accepted 24 May 2015

Academic Editor: Mehdi Chenik

Copyright © 2015 Jose M. Requena et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. N. Vonlaufen, S. M. Kanzok, R. C. Wek, and W. J. Sullivan Jr., “Stress response pathways in protozoan parasites,” Cellular Microbiology, vol. 10, no. 12, pp. 2387–2399, 2008. View at Publisher · View at Google Scholar · View at Scopus
  2. A. Shonhai, A. G. Maier, J. M. Przyborski, and G. L. Blatch, “Intracellular protozoan parasites of humans: the role of molecular chaperones in development and pathogenesis,” Protein and Peptide Letters, vol. 18, no. 2, pp. 143–157, 2011. View at Publisher · View at Google Scholar · View at Scopus
  3. B. S. McGwire and A. R. Satoskar, “Leishmaniasis: clinical syndromes and treatment,” QJM, vol. 107, no. 1, pp. 7–14, 2013. View at Publisher · View at Google Scholar
  4. J. Alvar, I. D. Vélez, C. Bern et al., “Leishmaniasis worldwide and global estimates of its incidence,” PLoS ONE, vol. 7, no. 5, Article ID e35671, 2012. View at Publisher · View at Google Scholar · View at Scopus
  5. A.-L. Bañuls, M. Hide, and F. Prugnolle, “Leishmania and the leishmaniases: a parasite genetic update and advances in taxonomy, epidemiology and pathogenicity in humans,” Advances in Parasitology, vol. 64, pp. 455–458, 2007. View at Publisher · View at Google Scholar · View at Scopus
  6. J. M. Requena, “The stressful life of pathogenic Leishmania species,” in Stress Response in Microbiology, J. M. Requena, Ed., 2012. View at Google Scholar
  7. M. Soto, L. Ramírez, M. A. Pineda et al., “Searching genes encoding Leishmania antigens for diagnosis and protection,” Scholarly Research Exchange, vol. 2009, Article ID 173039, 25 pages, 2009. View at Publisher · View at Google Scholar · View at Scopus
  8. K. Tamura, G. Stecher, D. Peterson, A. Filipski, and S. Kumar, “MEGA6: molecular evolutionary genetics analysis version 6.0,” Molecular Biology and Evolution, vol. 30, no. 12, pp. 2725–2729, 2013. View at Publisher · View at Google Scholar · View at Scopus
  9. J. Frydman, “Folding of newly translated proteins in vivo: the role of molecular chaperones,” Annual Review of Biochemistry, vol. 70, pp. 603–648, 2001. View at Publisher · View at Google Scholar · View at Scopus
  10. J. Verghese, J. Abrams, Y. Wang, and K. A. Morano, “Biology of the heat shock response and protein chaperones: budding yeast (Saccharomyces cerevisiae) as a model system,” Microbiology and Molecular Biology Reviews, vol. 76, no. 2, pp. 115–158, 2012. View at Publisher · View at Google Scholar · View at Scopus
  11. H. Saibil, “Chaperone machines for protein folding, unfolding and disaggregation,” Nature Reviews Molecular Cell Biology, vol. 14, no. 10, pp. 630–642, 2013. View at Publisher · View at Google Scholar · View at Scopus
  12. M. Brehme, C. Voisine, T. Rolland et al., “A chaperome subnetwork safeguards proteostasis in aging and neurodegenerative disease,” Cell Reports, vol. 9, no. 3, pp. 1135–1150, 2014. View at Publisher · View at Google Scholar
  13. T. Taldone, S. O. Ochiana, P. D. Patel, and G. Chiosis, “Selective targeting of the stress chaperome as a therapeutic strategy,” Trends in Pharmacological Sciences, vol. 35, no. 11, pp. 592–603, 2014. View at Publisher · View at Google Scholar
  14. S. Lindquist and E. A. Craig, “The heat-shock proteins,” Annual Review of Genetics, vol. 22, pp. 631–677, 1988. View at Publisher · View at Google Scholar · View at Scopus
  15. C. Folgueira and J. M. Requena, “A postgenomic view of the heat shock proteins in kinetoplastids,” FEMS Microbiology Reviews, vol. 31, no. 4, pp. 359–377, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. H. H. Kampinga and E. A. Craig, “The HSP70 chaperone machinery: J proteins as drivers of functional specificity,” Nature Reviews Molecular Cell Biology, vol. 11, no. 8, pp. 579–592, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. T. R. Barends, N. D. Werbeck, and J. Reinstein, “Disaggregases in 4 dimensions,” Current Opinion in Structural Biology, vol. 20, no. 1, pp. 46–53, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. E. Basha, H. O'Neill, and E. Vierling, “Small heat shock proteins and α-crystallins: dynamic proteins with flexible functions,” Trends in Biochemical Sciences, vol. 37, no. 3, pp. 106–117, 2012. View at Publisher · View at Google Scholar · View at Scopus
  19. P. I. Hanson and S. W. Whiteheart, “AAA+ proteins: have engine, will work,” Nature Reviews Molecular Cell Biology, vol. 6, no. 7, pp. 519–529, 2005. View at Publisher · View at Google Scholar · View at Scopus
  20. M. P. Mayer, “Gymnastics of molecular chaperones,” Molecular Cell, vol. 39, no. 3, pp. 321–331, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. S. Lee, M. E. Sowa, J.-M. Choi, and F. T. F. Tsai, “The ClpB/Hsp104 molecular chaperone—a protein disaggregating machine,” Journal of Structural Biology, vol. 146, no. 1-2, pp. 99–105, 2004. View at Publisher · View at Google Scholar · View at Scopus
  22. K. Richter, M. Haslbeck, and J. Buchner, “The heat shock response: life on the verge of death,” Molecular Cell, vol. 40, no. 2, pp. 253–266, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. A. Schaupp, M. Marcinowski, V. Grimminger, B. Bösl, and S. Walter, “Processing of proteins by the molecular chaperone Hsp104,” Journal of Molecular Biology, vol. 370, no. 4, pp. 674–686, 2007. View at Publisher · View at Google Scholar · View at Scopus
  24. J. Shorter and S. Lindquist, “Prions as adaptive conduits of memory and inheritance,” Nature Reviews Genetics, vol. 6, no. 6, pp. 435–450, 2005. View at Publisher · View at Google Scholar · View at Scopus
  25. A. Hubel, S. Brandau, A. Dresel, and J. Clos, “A member of the ClpB family of stress proteins is expressed during heat shock in Leishmania spp.,” Molecular and Biochemical Parasitology, vol. 70, no. 1-2, pp. 107–118, 1995. View at Publisher · View at Google Scholar · View at Scopus
  26. A. Hübel, S. Krobitsch, A. Hörauf, and J. Clos, “Leishmania major Hsp100 is required chiefly in the mammalian stage of the parasite,” Molecular and Cellular Biology, vol. 17, no. 10, pp. 5987–5995, 1997. View at Google Scholar · View at Scopus
  27. L. Reiling, T. Jacobs, M. Kroemer, I. Gaworski, S. Graefe, and J. Clos, “Spontaneous recovery of pathogenicity by Leishmania major hsp100-/- alters the immune response in mice,” Infection and Immunity, vol. 74, no. 11, pp. 6027–6036, 2006. View at Publisher · View at Google Scholar · View at Scopus
  28. S. Krobitsch and J. Clos, “A novel role for 100 kD heat shock proteins in the parasite Leishmania donovani,” Cell Stress and Chaperones, vol. 4, no. 3, pp. 191–198, 1999. View at Publisher · View at Google Scholar · View at Scopus
  29. J. M. Silverman, J. Clos, E. Horakova et al., “Leishmania exosomes modulate innate and adaptive immune responses through effects on monocytes and dendritic cells,” Journal of Immunology, vol. 185, no. 9, pp. 5011–5022, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. D. Missiakas, F. Schwager, J.-M. Betton, C. Georgopoulos, and S. Raina, “Identification and characterization of HsIV HsIU (ClpQ ClpY) proteins involved in overall proteolysis of misfolded proteins in Escherichia coli,” The EMBO Journal, vol. 15, no. 24, pp. 6899–6909, 1996. View at Google Scholar · View at Scopus
  31. Z. Li, M. E. Lindsay, S. A. Motyka, P. T. Englund, and C. C. Wang, “Identification of a bacterial-like HslVU protease in the mitochondria of Trypanosoma brucei and its role in mitochondrial DNA replication,” PLoS Pathogens, vol. 4, no. 4, Article ID e1000048, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. M. Chrobak, S. Förster, S. Meisel, R. Pfefferkorn, F. Förster, and J. Clos, “Leishmania donovani HslV does not interact stably with HslU proteins,” International Journal for Parasitology, vol. 42, no. 4, pp. 329–339, 2012. View at Publisher · View at Google Scholar · View at Scopus
  33. D.-E. Mbang-Benet, Y. Sterkers, C. Morelle et al., “The bacterial-like HslVU protease complex subunits are involved in the control of different cell cycle events in trypanosomatids,” Acta Tropica, vol. 131, no. 1, pp. 22–31, 2014. View at Publisher · View at Google Scholar · View at Scopus
  34. L. H. Pearl, C. Prodromou, and P. Workman, “The Hsp90 molecular chaperone: an open and shut case for treatment,” Biochemical Journal, vol. 410, no. 3, pp. 439–453, 2008. View at Publisher · View at Google Scholar · View at Scopus
  35. J. L. Johnson, “Evolution and function of diverse Hsp90 homologs and cochaperone proteins,” Biochimica et Biophysica Acta, vol. 1823, no. 3, pp. 607–613, 2012. View at Publisher · View at Google Scholar · View at Scopus
  36. M. Stankiewicz and M. P. Mayer, “The universe of Hsp90,” BioMolecular Concepts, vol. 3, no. 1, pp. 79–97, 2012. View at Publisher · View at Google Scholar
  37. J. Lachowiec, T. Lemus, E. Borenstein, and C. Queitsch, “Hsp90 promotes kinase evolution,” Molecular Biology and Evolution, vol. 32, no. 1, pp. 91–99, 2014. View at Publisher · View at Google Scholar
  38. M. Taipale, D. F. Jarosz, and S. Lindquist, “HSP90 at the hub of protein homeostasis: emerging mechanistic insights,” Nature Reviews Molecular Cell Biology, vol. 11, no. 7, pp. 515–528, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. A. Röhl, J. Rohrberg, and J. Buchner, “The chaperone Hsp90: changing partners for demanding clients,” Trends in Biochemical Sciences, vol. 38, no. 5, pp. 253–262, 2013. View at Publisher · View at Google Scholar · View at Scopus
  40. C. E. Stebbins, A. A. Russo, C. Schneider, N. Rosen, F. U. Hartl, and N. P. Pavletich, “Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent,” Cell, vol. 89, no. 2, pp. 239–250, 1997. View at Publisher · View at Google Scholar · View at Scopus
  41. G. E. Karagöz and S. G. Rüdiger, “Hsp90 interaction with clients,” Trends in Biochemical Sciences, vol. 40, no. 2, pp. 117–125, 2015. View at Publisher · View at Google Scholar
  42. J. Li, J. Soroka, and J. Buchner, “The Hsp90 chaperone machinery: conformational dynamics and regulation by co-chaperones,” Biochimica et Biophysica Acta—Molecular Cell Research, vol. 1823, no. 3, pp. 624–635, 2012. View at Publisher · View at Google Scholar · View at Scopus
  43. M. Mollapour and L. Neckers, “Post-translational modifications of Hsp90 and their contributions to chaperone regulation,” Biochimica et Biophysica Acta, vol. 1823, no. 3, pp. 648–655, 2012. View at Publisher · View at Google Scholar · View at Scopus
  44. J. Li and J. Buchner, “Structure, function and regulation of the Hsp90 machinery,” Biomedical Journal, vol. 36, no. 3, pp. 106–117, 2013. View at Publisher · View at Google Scholar · View at Scopus
  45. L. H. T. Van der Ploeg, S. H. Giannini, and C. R. Cantor, “Heat shock genes: regulatory role for differentiation in parasitic protozoa,” Science, vol. 228, no. 4706, pp. 1443–1446, 1985. View at Publisher · View at Google Scholar · View at Scopus
  46. S. Brandau, A. Dresel, and J. Clos, “High constitutive levels of heat-shock proteins-in human-pathogenic parasites of the genus Leishmania,” Biochemical Journal, vol. 310, no. 1, pp. 225–232, 1995. View at Google Scholar · View at Scopus
  47. R. Larreta, M. Soto, C. Alonso, and J. M. Requena, “Leishmania infantum: gene cloning of the GRP94 homologue, its expression as recombinant protein, and analysis of antigenicity,” Experimental Parasitology, vol. 96, no. 2, pp. 108–115, 2000. View at Publisher · View at Google Scholar · View at Scopus
  48. A. Descoteaux, H. A. Avila, K. Zhang, S. J. Turco, and S. M. Beverley, “Leishmania LPG3 encodes a GRP94 homolog required for phosphoglycan synthesis implicated in parasite virulence but not viability,” The EMBO Journal, vol. 21, no. 17, pp. 4458–4469, 2002. View at Publisher · View at Google Scholar · View at Scopus
  49. P. C. Echeverria, M. Matrajt, O. S. Harb et al., “Toxoplasma gondii Hsp90 is a potential drug target whose expression and subcellular localization are developmentally regulated,” Journal of Molecular Biology, vol. 350, no. 4, pp. 723–734, 2005. View at Publisher · View at Google Scholar · View at Scopus
  50. N. Roy, R. K. Nageshan, S. Ranade, and U. Tatu, “Heat shock protein 90 from neglected protozoan parasites,” Biochimica et Biophysica Acta—Molecular Cell Research, vol. 1823, no. 3, pp. 707–711, 2012. View at Publisher · View at Google Scholar · View at Scopus
  51. M. Wiesgigl and J. Clos, “Heat shock protein 90 homeostasis controls stage differentiation in Leishmania donovani,” Molecular Biology of the Cell, vol. 12, no. 11, pp. 3307–3316, 2001. View at Publisher · View at Google Scholar · View at Scopus
  52. K. P. Silva, T. V. Seraphim, and J. C. Borges, “Structural and functional studies of Leishmania braziliensis Hsp90,” Biochimica et Biophysica Acta, vol. 1834, no. 1, pp. 351–361, 2013. View at Publisher · View at Google Scholar · View at Scopus
  53. R. Larreta, M. Soto, L. Quijada et al., “The expression of HSP83 genes in Leishmania infantum is affected by temperature and by stage-differentiation and is regulated at the levels of mRNA stability and translation,” BMC Molecular Biology, vol. 5, no. 1, article 3, 2004. View at Publisher · View at Google Scholar · View at Scopus
  54. A. Hombach and J. Clos, “No stress—Hsp90 and signal transduction in Leishmania,” Parasitology, vol. 141, no. 9, pp. 1156–1166, 2014. View at Publisher · View at Google Scholar · View at Scopus
  55. M. J. Figueras, P. C. Echeverria, and S. O. Angel, “Protozoan HSP90-heterocomplex: molecular interaction network and biological significance,” Current Protein & Peptide Science, vol. 15, no. 3, pp. 245–255, 2014. View at Publisher · View at Google Scholar
  56. J. R. Webb, A. Campos-Neto, Y. A. W. Skeiky, and S. G. Reed, “Molecular characterization of the heat-inducible LmSTI1 protein of Leishmania major,” Molecular and Biochemical Parasitology, vol. 89, no. 2, pp. 179–193, 1997. View at Publisher · View at Google Scholar · View at Scopus
  57. M. A. Morales, R. Watanabe, M. Dacher et al., “Phosphoproteome dynamics reveal heat-shock protein complexes specific to the Leishmania donovani infectious stage,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 18, pp. 8381–8386, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. A. Hombach, G. Ommen, M. Chrobak, and J. Clos, “The Hsp90-Sti1 interaction is critical for Leishmania donovani proliferation in both life cycle stages,” Cellular Microbiology, vol. 15, no. 4, pp. 585–600, 2013. View at Publisher · View at Google Scholar · View at Scopus
  59. C.-T. Lee, C. Graf, F. J. Mayer, S. M. Richter, and M. P. Mayer, “Dynamics of the regulation of Hsp90 by the co-chaperone Sti1,” The EMBO Journal, vol. 31, no. 6, pp. 1518–1528, 2012. View at Publisher · View at Google Scholar · View at Scopus
  60. G. Ommen, S. Lorenz, and J. Clos, “One-step generation of double-allele gene replacement mutants in Leishmania donovani,” International Journal for Parasitology, vol. 39, no. 5, pp. 541–546, 2009. View at Publisher · View at Google Scholar · View at Scopus
  61. G. Ommen, M. Chrobak, and J. Clos, “The co-chaperone sgt of Leishmania donovani is essential for the parasite's viability,” Cell Stress and Chaperones, vol. 15, no. 4, pp. 443–455, 2010. View at Publisher · View at Google Scholar · View at Scopus
  62. P. Meyer, C. Prodromou, B. Hu et al., “Structural and functional analysis of the middle segment of Hsp90: implications for ATP hydrolysis and client protein and cochaperone interactions,” Molecular Cell, vol. 11, no. 3, pp. 647–658, 2003. View at Publisher · View at Google Scholar · View at Scopus
  63. T. V. Seraphim, M. M. Alves, I. M. Silva et al., “Low resolution structural studies indicate that the activator of Hsp90 ATPase 1 (Aha1) of Leishmania braziliensis has an elongated shape which allows its interaction with both N- and M-domains of Hsp90,” PLoS ONE, vol. 8, no. 6, Article ID e66822, 2013. View at Publisher · View at Google Scholar · View at Scopus
  64. F. A. H. Batista, G. S. Almeida, T. V. Seraphim et al., “Identification of two p23 co-chaperone isoforms in Leishmania braziliensis exhibiting similar structures and Hsp90 interaction properties despite divergent stabilities,” The FEBS Journal, vol. 282, no. 2, pp. 388–406, 2015. View at Publisher · View at Google Scholar
  65. A. J. Caplan, “Hsp90's secrets unfold: new insights from structural and functional studies,” Trends in Cell Biology, vol. 9, no. 7, pp. 262–268, 1999. View at Publisher · View at Google Scholar · View at Scopus
  66. S. Barik, “Immunophilins: for the love of proteins,” Cellular and Molecular Life Sciences, vol. 63, no. 24, pp. 2889–2900, 2006. View at Publisher · View at Google Scholar · View at Scopus
  67. W.-L. Yau, T. Blisnick, J.-F. Taly et al., “Cyclosporin A treatment of Leishmania donovani reveals stage-specific functions of cyclophilins in parasite proliferation and viability,” PLoS Neglected Tropical Diseases, vol. 4, no. 6, article e729, 2010. View at Publisher · View at Google Scholar · View at Scopus
  68. W. L. Yau, P. Pescher, A. MacDonald et al., “The Leishmania donovani chaperone cyclophilin 40 is essential for intracellular infection independent of its stage-specific phosphorylation status,” Molecular Microbiology, vol. 93, no. 1, pp. 80–97, 2014. View at Publisher · View at Google Scholar
  69. M.-A. Adriano, B. Vergnes, J. Poncet et al., “Proof of interaction between Leishmania SIR2RP1 deacetylase and chaperone HSP83,” Parasitology Research, vol. 100, no. 4, pp. 811–818, 2007. View at Publisher · View at Google Scholar · View at Scopus
  70. J. A. García-Salcedo, P. Gijón, D. P. Nolan, P. Tebabi, and E. Pays, “A chromosomal SIR2 homologue with both histone NAD-dependent ADP-ribosyltransferase and deacetylase activities is involved in DNA repair in Trypanosoma brucei,” The EMBO Journal, vol. 22, no. 21, pp. 5851–5862, 2003. View at Publisher · View at Google Scholar · View at Scopus
  71. B. Vergnes, D. Sereno, J. Tavares et al., “Targeted disruption of cytosolic SIR2 deacetylase discloses its essential role in Leishmania survival and proliferation,” Gene, vol. 363, no. 1-2, pp. 85–96, 2005. View at Publisher · View at Google Scholar · View at Scopus
  72. K. T. Riabowol, L. A. Mizzen, and W. J. Welch, “Heat shock is lethal to fibroblasts microinjected with antibodies against hsp70,” Science, vol. 242, no. 4877, pp. 433–436, 1988. View at Publisher · View at Google Scholar · View at Scopus
  73. M. P. Mayer and B. Bukau, “Hsp70 chaperones: cellular functions and molecular mechanism,” Cellular and Molecular Life Sciences, vol. 62, no. 6, pp. 670–684, 2005. View at Publisher · View at Google Scholar · View at Scopus
  74. M. Daugaard, M. Rohde, and M. Jäättelä, “The heat shock protein 70 family: highly homologous proteins with overlapping and distinct functions,” FEBS Letters, vol. 581, no. 19, pp. 3702–3710, 2007. View at Publisher · View at Google Scholar · View at Scopus
  75. R. M. Vabulas, S. Raychaudhuri, M. Hayer-Hartl, and F. U. Hartl, “Protein folding in the cytoplasm and the heat shock response,” Cold Spring Harbor perspectives in biology, vol. 2, no. 12, Article ID a004390, 2010. View at Google Scholar · View at Scopus
  76. R. S. Gupta, “Protein phylogenies and signature sequences: evolutionary relationships within prokaryotes and between prokaryotes and eukaryotes,” Antonie Van Leeuwenhoek, vol. 72, no. 1, pp. 49–61, 1997. View at Publisher · View at Google Scholar · View at Scopus
  77. M. Kabani and C. N. Martineau, “Multiple Hsp70 isoforms in the eukaryotic cytosol: mere redundancy or functional specificity?” Current Genomics, vol. 9, no. 5, pp. 338–348, 2008. View at Publisher · View at Google Scholar · View at Scopus
  78. P. Genevaux, C. Georgopoulos, and W. L. Kelley, “The Hsp70 chaperone machines of Escherichia coli: a paradigm for the repartition of chaperone functions,” Molecular Microbiology, vol. 66, no. 4, pp. 840–857, 2007. View at Publisher · View at Google Scholar · View at Scopus
  79. A. Shonhai, A. Boshoff, and G. L. Blatch, “The structural and functional diversity of Hsp70 proteins from Plasmodium falciparum,” Protein Science, vol. 16, no. 9, pp. 1803–1818, 2007. View at Publisher · View at Google Scholar · View at Scopus
  80. D. P. Easton, Y. Kaneko, and J. R. Subjeck, “The Hsp110 and Grp170 stress proteins: newly recognized relatives of the Hsp70s,” Cell Stress and Chaperones, vol. 5, no. 4, pp. 276–290, 2000. View at Publisher · View at Google Scholar · View at Scopus
  81. L. Shaner and K. A. Morano, “All in the family: atypical Hsp70 chaperones are conserved modulators of Hsp70 activity,” Cell Stress and Chaperones, vol. 12, no. 1, pp. 1–8, 2007. View at Publisher · View at Google Scholar · View at Scopus
  82. J. C. Young, “Mechanisms of the Hsp70 chaperone system,” Biochemistry and Cell Biology, vol. 88, no. 2, pp. 291–300, 2010. View at Publisher · View at Google Scholar · View at Scopus
  83. K. P. da Silva and J. C. Borges, “The molecular chaperone Hsp70 family members function by a bidirectional heterotrophic allosteric mechanism,” Protein and Peptide Letters, vol. 18, no. 2, pp. 132–142, 2011. View at Publisher · View at Google Scholar · View at Scopus
  84. J. F. Swain, G. Dinler, R. Sivendran, D. L. Montgomery, M. Stotz, and L. M. Gierasch, “Hsp70 chaperone ligands control domain association via an allosteric mechanism mediated by the interdomain linker,” Molecular Cell, vol. 26, no. 1, pp. 27–39, 2007. View at Publisher · View at Google Scholar · View at Scopus
  85. G. L. Blatch and M. Lässle, “The tetratricopeptide repeat: a structural motif mediating protein-protein interactions,” BioEssays, vol. 21, no. 11, pp. 932–939, 1999. View at Publisher · View at Google Scholar · View at Scopus
  86. C. Scheufler, A. Brinker, G. Bourenkov et al., “Structure of TPR domain-peptide complexes: critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine,” Cell, vol. 101, no. 2, pp. 199–210, 2000. View at Publisher · View at Google Scholar · View at Scopus
  87. M. P. Mayer, “Hsp70 chaperone dynamics and molecular mechanism,” Trends in Biochemical Sciences, vol. 38, no. 10, pp. 507–514, 2013. View at Publisher · View at Google Scholar · View at Scopus
  88. J. S. McCarty, A. Buchberger, J. Reinstein, and B. Bukau, “The role of ATP in the functional cycle of the DnaK chaperone system,” Journal of Molecular Biology, vol. 249, no. 1, pp. 126–137, 1995. View at Publisher · View at Google Scholar · View at Scopus
  89. P. Goloubinoff and P. D. L. Rios, “The mechanism of Hsp70 chaperones: (entropic) pulling the models together,” Trends in Biochemical Sciences, vol. 32, no. 8, pp. 372–380, 2007. View at Publisher · View at Google Scholar · View at Scopus
  90. T. Laufen, M. P. Mayer, C. Beisel et al., “Mechanism of regulation of Hsp70 chaperones by DnaJ cochaperones,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 10, pp. 5452–5457, 1999. View at Publisher · View at Google Scholar · View at Scopus
  91. S. Tzankov, M. J. H. Wong, K. Shi, C. Nassif, and J. C. Young, “Functional divergence between co-chaperones of Hsc70,” The Journal of Biological Chemistry, vol. 283, no. 40, pp. 27100–27109, 2008. View at Publisher · View at Google Scholar · View at Scopus
  92. T. Liu, C. K. Daniels, and S. Cao, “Comprehensive review on the HSC70 functions, interactions with related molecules and involvement in clinical diseases and therapeutic potential,” Pharmacology and Therapeutics, vol. 136, no. 3, pp. 354–374, 2012. View at Publisher · View at Google Scholar · View at Scopus
  93. J. Hohfeld, Y. Minami, and F.-U. Hartl, “Hip, a novel cochaperone involved in the eukaryotic Hsc70/Hsp40 reaction cycle,” Cell, vol. 83, no. 4, pp. 589–598, 1995. View at Publisher · View at Google Scholar · View at Scopus
  94. H. McDonough and C. Patterson, “CHIP: a link between the chaperone and proteasome systems,” Cell Stress and Chaperones, vol. 8, no. 4, pp. 303–308, 2003. View at Publisher · View at Google Scholar · View at Scopus
  95. P. R. Dores-Silva, E. R. Silva, F. E. R. Gomes, K. P. Silva, L. R. S. Barbosa, and J. C. Borges, “Low resolution structural characterization of the Hsp70-interacting protein—Hip—from Leishmania braziliensis emphasizes its high asymmetry,” Archives of Biochemistry and Biophysics, vol. 520, no. 2, pp. 88–98, 2012. View at Publisher · View at Google Scholar · View at Scopus
  96. S. Searle and D. F. Smith, “Leishmania major. Characterization and expression of a cytoplasmic stress related protein,” Experimental Parasitology, vol. 77, no. 1, pp. 43–52, 1993. View at Publisher · View at Google Scholar · View at Scopus
  97. D. Moreira, H. Le Guyader, and H. Philippe, “The origin of red algae and the evolution of chloroplasts,” Nature, vol. 405, no. 6782, pp. 69–72, 2000. View at Publisher · View at Google Scholar · View at Scopus
  98. V. Hannaert, E. Saavedra, F. Duffieux et al., “Plant-like traits associated with metabolism of Trypanosoma parasites,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 3, pp. 1067–1071, 2003. View at Publisher · View at Google Scholar · View at Scopus
  99. W. Martin and P. Borst, “Secondary loss of chloroplasts in trypanosomes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 3, pp. 765–767, 2003. View at Publisher · View at Google Scholar · View at Scopus
  100. C. A. Louw, M. H. Ludewig, J. Mayer, and G. L. Blatch, “The Hsp70 chaperones of the Tritryps are characterized by unusual features and novel members,” Parasitology International, vol. 59, no. 4, pp. 497–505, 2010. View at Publisher · View at Google Scholar · View at Scopus
  101. A. Burger, M. H. Ludewig, and A. Boshoff, “Investigating the chaperone properties of a novel heat shock protein, Hsp70.c, from Trypanosoma brucei,” Journal of Parasitology Research, vol. 2014, Article ID 172582, 12 pages, 2014. View at Publisher · View at Google Scholar · View at Scopus
  102. C. Folgueira, C. Cañavate, C. Chicharro, and J. M. Requena, “Genomic organization and expression of the HSP70 locus in New and Old World Leishmania species,” Parasitology, vol. 134, no. 3, pp. 369–377, 2007. View at Publisher · View at Google Scholar · View at Scopus
  103. C. A. Ramírez, J. M. Requena, and C. J. Puerta, “Identification of the HSP70-II gene in Leishmania braziliensis HSP70 locus: genomic organization and UTRs characterization,” Parasites & vectors, vol. 4, article 166, 2011. View at Publisher · View at Google Scholar · View at Scopus
  104. C. Folgueira, L. Quijada, M. Soto, D. R. Abanades, C. Alonso, and J. M. Requena, “The translational efficiencies of the two Leishmania infantum HSP70 mRNAs, differing in their 3′-untranslated regions, are affected by shifts in the temperature of growth through different mechanisms,” The Journal of Biological Chemistry, vol. 280, no. 42, pp. 35172–35183, 2005. View at Publisher · View at Google Scholar · View at Scopus
  105. C. Folgueira, J. Carrión, J. Moreno, J. M. Saugar, C. Cañavate, and J. M. Requena, “Effects of the disruption of the HSP70-II gene on the growth, morphology, and virulence of Leishmania infantum promastigotes,” International Microbiology, vol. 11, no. 2, pp. 81–89, 2008. View at Publisher · View at Google Scholar · View at Scopus
  106. M. A. Miller, S. E. McGowan, K. R. Gantt et al., “Inducible resistance to oxidant stress in the protozoan Leishmania chagasi,” The Journal of Biological Chemistry, vol. 275, no. 43, pp. 33883–33889, 2000. View at Publisher · View at Google Scholar · View at Scopus
  107. W. J. Netzer and F. U. Hartl, “Protein folding in the cytosol: chaperonin-dependent and -independent mechanisms,” Trends in Biochemical Sciences, vol. 23, no. 2, pp. 68–73, 1998. View at Publisher · View at Google Scholar · View at Scopus
  108. C. Spiess, A. S. Meyer, S. Reissmann, and J. Frydman, “Mechanism of the eukaryotic chaperonin: protein folding in the chamber of secrets,” Trends in Cell Biology, vol. 14, no. 11, pp. 598–604, 2004. View at Publisher · View at Google Scholar · View at Scopus
  109. S. Walter, “Structure and function of the GroE chaperone,” Cellular and Molecular Life Sciences, vol. 59, no. 10, pp. 1589–1597, 2002. View at Publisher · View at Google Scholar · View at Scopus
  110. Z. Xu, A. L. Horwich, and P. B. Sigler, “The crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonin complex,” Nature, vol. 388, no. 6644, pp. 741–750, 1997. View at Publisher · View at Google Scholar · View at Scopus
  111. D. K. Clare, D. Vasishtan, S. Stagg et al., “ATP-triggered conformational changes delineate substrate-binding and -folding mechanics of the GroEL chaperonin,” Cell, vol. 149, no. 1, pp. 113–123, 2012. View at Publisher · View at Google Scholar · View at Scopus
  112. A. L. Horwich, W. A. Fenton, E. Chapman, and G. W. Farr, “Two families of chaperonin: physiology and mechanism,” Annual Review of Cell and Developmental Biology, vol. 23, pp. 115–145, 2007. View at Publisher · View at Google Scholar · View at Scopus
  113. L. Ditzel, J. Löwe, D. Stock et al., “Crystal structure of the thermosome, the archaeal chaperonin and homolog of CCT,” Cell, vol. 93, no. 1, pp. 125–138, 1998. View at Publisher · View at Google Scholar · View at Scopus
  114. J. M. Valpuesta, J. Martín-Benito, P. Gómez-Puertas, J. L. Carrascosa, and K. R. Willison, “Structure and function of a protein folding machine: the eukaryotic cytosolic chaperonin CCT,” FEBS Letters, vol. 529, no. 1, pp. 11–16, 2002. View at Publisher · View at Google Scholar · View at Scopus
  115. J. A. Rey-Ladino, P. B. Joshi, B. Singh, R. Gupta, and N. E. Reiner, “Leishmania major: molecular cloning, sequencing, and expression of the heat shock protein 60 gene reveals unique carboxy terminal peptide sequences,” Experimental Parasitology, vol. 85, no. 3, pp. 249–263, 1997. View at Publisher · View at Google Scholar · View at Scopus
  116. A. Schlüter, M. Wiesgigl, C. Hoyer et al., “Expression and subcellular localization of cpn60 protein family members in Leishmania donovani,” Biochimica et Biophysica Acta, vol. 1491, no. 1–3, pp. 65–74, 2000. View at Publisher · View at Google Scholar · View at Scopus
  117. Y. Hu, B. Henderson, P. A. Lund et al., “A Mycobacterium tuberculosis mutant lacking the groEL homologue cpn60.1 is viable but fails to induce an inflammatory response in animal models of infection,” Infection and Immunity, vol. 76, no. 4, pp. 1535–1546, 2008. View at Publisher · View at Google Scholar · View at Scopus
  118. S. Sarkar and S. C. Lakhotia, “The Hsp60C gene in the 25F cytogenetic region in Drosophila melanogaster is essential for tracheal development and fertility,” Journal of Genetics, vol. 84, no. 3, pp. 265–281, 2005. View at Publisher · View at Google Scholar · View at Scopus
  119. F. B. Zamora-Veyl, M. Kroemer, D. Zander, and J. Clos, “Stage-specific expression of the mitochondrial co-chaperonin of Leishmania donovani, CPN10,” Kinetoplastid Biology and Disease, vol. 4, no. 1, article 3, 2005. View at Publisher · View at Google Scholar · View at Scopus
  120. T. Langer, C. Lu, H. Echols, J. Flanagan, M. K. Hayer, and F. U. Hartl, “Successive action of DnaK, DnaJ and GroEL along the pathway of chaperone-mediated protein folding,” Nature, vol. 356, no. 6371, pp. 683–689, 1992. View at Publisher · View at Google Scholar · View at Scopus
  121. X.-B. Qiu, Y.-M. Shao, S. Miao, and L. Wang, “The diversity of the DnaJ/Hsp40 family, the crucial partners for Hsp70 chaperones,” Cellular and Molecular Life Sciences, vol. 63, no. 22, pp. 2560–2570, 2006. View at Publisher · View at Google Scholar · View at Scopus
  122. M. Botha, E.-R. Pesce, and G. L. Blatch, “The Hsp40 proteins of Plasmodium falciparum and other apicomplexa: regulating chaperone power in the parasite and the host,” International Journal of Biochemistry & Cell Biology, vol. 39, no. 10, pp. 1781–1803, 2007. View at Publisher · View at Google Scholar · View at Scopus
  123. M. Rug and A. G. Maier, “The heat shock protein 40 family of the malaria parasite Plasmodium falciparum,” IUBMB Life, vol. 63, no. 12, pp. 1081–1086, 2011. View at Publisher · View at Google Scholar · View at Scopus
  124. P. Wittung-Stafshede, J. Guidry, B. E. Horne, and S. J. Landry, “The J-domain of Hsp40 couples ATP hydrolysis to substrate capture in Hsp70,” Biochemistry, vol. 42, no. 17, pp. 4937–4944, 2003. View at Publisher · View at Google Scholar · View at Scopus
  125. M. E. Cheetham and A. J. Caplan, “Structure, function and evolution of DnaJ: conservation and adaptation of chaperone function,” Cell Stress and Chaperones, vol. 3, no. 1, pp. 28–36, 1998. View at Google Scholar · View at Scopus
  126. P. Walsh, D. Bursać, Y. C. Law, D. Cyr, and T. Lithgow, “The J-protein family: modulating protein assembly, disassembly and translocation,” EMBO Reports, vol. 5, no. 6, pp. 567–571, 2004. View at Publisher · View at Google Scholar · View at Scopus
  127. F. Hennessy, W. S. Nicoll, R. Zimmermann, M. E. Cheetham, and G. L. Blatch, “Not all J domains are created equal: implications for the specificity of Hsp40-Hsp70 interactions,” Protein Science, vol. 14, no. 7, pp. 1697–1709, 2005. View at Publisher · View at Google Scholar · View at Scopus
  128. P. Tsigankov, P. F. Gherardini, M. Helmer-Citterich, G. F. Spath, P. J. Myler, and D. Zilberstein, “Regulation dynamics of Leishmania differentiation: deconvoluting signals and identifying phosphorylation trends,” Molecular & Cellular Proteomics, vol. 13, no. 7, pp. 1787–1799, 2014. View at Publisher · View at Google Scholar
  129. T. Kriehuber, T. Rattei, T. Weinmaier, A. Bepperling, M. Haslbeck, and J. Buchner, “Independent evolution of the core domain and its flanking sequences in small heat shock proteins,” The FASEB Journal, vol. 24, no. 10, pp. 3633–3642, 2010. View at Publisher · View at Google Scholar · View at Scopus
  130. M. Haslbeck, T. Franzmann, D. Weinfurtner, and J. Buchner, “Some like it hot: the structure and function of small heat-shock proteins,” Nature Structural & Molecular Biology, vol. 12, no. 10, pp. 842–846, 2005. View at Publisher · View at Google Scholar · View at Scopus
  131. Y. Sun and T. H. MacRae, “Small heat shock proteins: molecular structure and chaperone function,” Cellular and Molecular Life Sciences, vol. 62, no. 21, pp. 2460–2476, 2005. View at Publisher · View at Google Scholar · View at Scopus
  132. H. Nakamoto and L. Vígh, “The small heat shock proteins and their clients,” Cellular and Molecular Life Sciences, vol. 64, no. 3, pp. 294–306, 2007. View at Publisher · View at Google Scholar · View at Scopus
  133. I. Horváth, G. Multhoff, A. Sonnleitner, and L. Vígh, “Membrane-associated stress proteins: more than simply chaperones,” Biochimica et Biophysica Acta, vol. 1778, no. 7-8, pp. 1653–1664, 2008. View at Publisher · View at Google Scholar · View at Scopus
  134. L. Zeng, J. Tan, T. Lu, Q. Lei, C. Chen, and Z. Hu, “Small heat shock proteins and the endoplasmic reticulum: potential attractive therapeutic targets?” Current Molecular Medicine, vol. 15, no. 1, pp. 38–46, 2015. View at Publisher · View at Google Scholar
  135. A. M. Montalvo-Álvarez, C. Folgueira, J. Carrión, L. Monzote-Fidalgo, C. Cañavate, and J. M. Requena, “The Leishmania HSP20 is antigenic during natural infections, but, as DNA vaccine, it does not protect BALB/c mice against experimental L. amazonensis infection,” Journal of Biomedicine and Biotechnology, vol. 2008, Article ID 695432, 9 pages, 2008. View at Publisher · View at Google Scholar · View at Scopus
  136. A. Hombach, G. Ommen, A. MacDonald, and J. Clos, “A small heat shock protein is essential for thermotolerance and intracellular survival of Leishmania donovani,” Journal of Cell Science, vol. 127, no. 21, pp. 4762–4773, 2014. View at Publisher · View at Google Scholar
  137. R. L. M. van Montfort, E. Basha, K. L. Friedrich, C. Slingsby, and E. Vierling, “Crystal structure and assembly of a eukaryotic small heat shock protein,” Nature Structural Biology, vol. 8, no. 12, pp. 1025–1030, 2001. View at Publisher · View at Google Scholar · View at Scopus
  138. J. J. M. Bergeron, M. B. Brenner, D. Y. Thomas, and D. B. Williams, “Calnexin: a membrane-bound chaperone of the endoplasmic reticulum,” Trends in Biochemical Sciences, vol. 19, no. 3, pp. 124–128, 1994. View at Publisher · View at Google Scholar · View at Scopus
  139. A. Helenius, E. S. Trombetta, D. N. Hebert, and J. F. Simons, “Calnexin, calreticulin and the folding of glycoproteins,” Trends in Cell Biology, vol. 7, no. 5, pp. 193–200, 1997. View at Publisher · View at Google Scholar · View at Scopus
  140. S. Dolai and S. Adak, “Endoplasmic reticulum stress responses in Leishmania,” Molecular and Biochemical Parasitology, vol. 197, no. 1-2, pp. 1–8, 2014. View at Publisher · View at Google Scholar
  141. L.-I. McCall and G. Matlashewski, “Localization and induction of the A2 virulence factor in Leishmania: evidence that A2 is a stress response protein,” Molecular Microbiology, vol. 77, no. 2, pp. 518–530, 2010. View at Publisher · View at Google Scholar · View at Scopus
  142. S. Dolai, S. Pal, R. K. Yadav, and S. Adak, “Endoplasmic reticulum stress-induced apoptosis in leishmania through Ca2+-dependent and caspase-independent mechanism,” The Journal of Biological Chemistry, vol. 286, no. 15, pp. 13638–13646, 2011. View at Publisher · View at Google Scholar · View at Scopus
  143. A. Debrabant, N. Lee, G. P. Pogue, D. M. Dwyer, and H. L. Nakhasi, “Expression of calreticulin P-domain results in impairment of secretory pathway in Leishmania donovani and reduced parasite survival in macrophages,” International Journal for Parasitology, vol. 32, no. 11, pp. 1423–1434, 2002. View at Publisher · View at Google Scholar · View at Scopus
  144. A. Padilla, R. Noiva, N. Lee, K. V. K. Mohan, H. L. Nakhasi, and A. Debrabant, “An atypical protein disulfide isomerase from the protozoan parasite Leishmania containing a single thioredoxin-like domain,” Journal of Biological Chemistry, vol. 278, no. 3, pp. 1872–1878, 2003. View at Publisher · View at Google Scholar · View at Scopus
  145. J. Rassow and N. Pfanner, “The protein import machinery of the mitochondrial membranes,” Traffic, vol. 1, no. 6, pp. 457–464, 2000. View at Publisher · View at Google Scholar · View at Scopus
  146. W. Voos, “Chaperone-protease networks in mitochondrial protein homeostasis,” Biochimica et Biophysica Acta, vol. 1833, no. 2, pp. 388–399, 2013. View at Publisher · View at Google Scholar · View at Scopus
  147. M. Falah and R. S. Gupta, “Cloning of the hsp70 (dnaK) genes from Rhizobium meliloti and Pseudomonas cepacia: phylogenetic analyses of mitochondrial origin based on a highly conserved protein sequence,” Journal of Bacteriology, vol. 176, no. 24, pp. 7748–7753, 1994. View at Google Scholar · View at Scopus
  148. R. M. Campos, M. Nascimento, J. C. Ferraz et al., “Distinct mitochondrial HSP70 homologues conserved in various Leishmania species suggest novel biological functions,” Molecular and Biochemical Parasitology, vol. 160, no. 2, pp. 157–162, 2008. View at Publisher · View at Google Scholar · View at Scopus
  149. J. Týč, M. M. Klingbeil, and J. Lukeš, “Mitochondrial heat shock protein machinery Hsp70/Hsp40 is indispensable for proper mitochondrial DNA maintenance and replication,” mBio, vol. 6, no. 1, 2015. View at Publisher · View at Google Scholar
  150. F. Teixeira, H. Castro, T. Cruz et al., “Mitochondrial peroxiredoxin functions as crucial chaperone reservoir in Leishmania infantum,” Proceedings of the National Academy of Sciences, vol. 112, no. 7, pp. E616–E624, 2015. View at Publisher · View at Google Scholar
  151. A. Hall, P. A. Karplus, and L. B. Poole, “Typical 2-Cys peroxiredoxins—structures, mechanisms and functions,” FEBS Journal, vol. 276, no. 9, pp. 2469–2477, 2009. View at Publisher · View at Google Scholar · View at Scopus
  152. H. Castro, F. Teixeira, S. Romao et al., “Leishmania mitochondrial peroxiredoxin plays a crucial peroxidase-unrelated role during infection: insight into its novel chaperone activity,” PLoS Pathogens, vol. 7, no. 10, Article ID e1002325, 2011. View at Publisher · View at Google Scholar · View at Scopus
  153. M. V. Powers, K. Jones, C. Barillari, I. Westwood, R. L. M. Van Montfort, and P. Workman, “Targeting HSP70: the second potentially druggable heat shock protein and molecular chaperone?” Cell Cycle, vol. 9, no. 8, pp. 1542–1550, 2010. View at Publisher · View at Google Scholar · View at Scopus
  154. A. L. D. O. A. Petersen, C. E. S. Guedes, C. L. Versoza et al., “17-AAG Kills intracellular Leishmania amazonensis while reducing inflammatory responses in infected macrophages,” PLoS ONE, vol. 7, no. 11, Article ID e49496, 2012. View at Publisher · View at Google Scholar · View at Scopus
  155. R. E. Varela-M, C. Mollinedo-Gajate, A. Muro, and F. Mollinedo, “The HSP90 inhibitor 17-AAG potentiates the antileishmanial activity of the ether lipid edelfosine,” Acta Tropica, vol. 131, no. 1, pp. 32–36, 2014. View at Publisher · View at Google Scholar · View at Scopus
  156. R. Garcia-Carbonero, A. Carnero, and L. Paz-Ares, “Inhibition of HSP90 molecular chaperones: moving into the clinic,” The Lancet Oncology, vol. 14, no. 9, pp. e358–e369, 2013. View at Publisher · View at Google Scholar · View at Scopus
  157. R. Pallavi, N. Roy, R. K. Nageshan et al., “Heat shock protein 90 as a drug target against protozoan infections: biochemical characterization of HSP90 from Plasmodium falciparum and Trypanosoma evansi and evaluation of its inhibitor as a candidate drug,” The Journal of Biological Chemistry, vol. 285, no. 49, pp. 37964–37975, 2010. View at Publisher · View at Google Scholar · View at Scopus
  158. D. M. Santos, A. L. Petersen, F. S. Celes et al., “Chemotherapeutic potential of 17-AAG against cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis,” PLoS Neglected Tropical Diseases, vol. 8, no. 10, Article ID e3275, 2014. View at Publisher · View at Google Scholar
  159. S. L. Croft, S. Sundar, and A. H. Fairlamb, “Drug resistance in leishmaniasis,” Clinical Microbiology Reviews, vol. 19, no. 1, pp. 111–126, 2006. View at Publisher · View at Google Scholar · View at Scopus
  160. C. Brochu, A. Halmeur, and M. Ouellette, “The heat shock protein HSP70 and heat shock cognate protein HSC70 contribute to antimony tolerance in the protozoan parasite Leishmania,” Cell Stress and Chaperones, vol. 9, no. 3, pp. 294–303, 2004. View at Publisher · View at Google Scholar · View at Scopus
  161. N. Biyani, A. K. Singh, S. Mandal, B. Chawla, and R. Madhubala, “Differential expression of proteins in antimony-susceptible and -resistant isolates of Leishmania donovani,” Molecular and Biochemical Parasitology, vol. 179, no. 2, pp. 91–99, 2011. View at Publisher · View at Google Scholar · View at Scopus
  162. A. Kumar, B. Sisodia, P. Misra, S. Sundar, A. K. Shasany, and A. Dube, “Proteome mapping of overexpressed membrane-enriched and cytosolic proteins in sodium antimony gluconate (SAG) resistant clinical isolate of Leishmania donovani,” British Journal of Clinical Pharmacology, vol. 70, no. 4, pp. 609–617, 2010. View at Publisher · View at Google Scholar · View at Scopus
  163. B. Vergnes, B. Gourbal, I. Girard, S. Sundar, J. Drummelsmith, and M. Ouellette, “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,” Molecular and Cellular Proteomics, vol. 6, no. 1, pp. 88–101, 2007. View at Publisher · View at Google Scholar · View at Scopus
  164. D. Sereno, P. Holzmuller, I. Mangot, G. Cuny, A. Ouaissi, and J.-L. Lemesre, “Antimonial-mediated DNA fragmentation in Leishmania infantum amastigotes,” Antimicrobial Agents and Chemotherapy, vol. 45, no. 7, pp. 2064–2069, 2001. View at Publisher · View at Google Scholar · View at Scopus
  165. C. Paris, P. M. Loiseau, C. Bories, and J. Bréard, “Miltefosine induces apoptosis-like death in Leishmania donovani promastigotes,” Antimicrobial Agents and Chemotherapy, vol. 48, no. 3, pp. 852–859, 2004. View at Publisher · View at Google Scholar · View at Scopus
  166. R. Arya, M. Mallik, and S. C. Lakhotia, “Heat shock genes—integrating cell survival and death,” Journal of Biosciences, vol. 32, no. 3, pp. 595–610, 2007. View at Publisher · View at Google Scholar · View at Scopus
  167. A. Alexandratos, J. Clos, M. Samiotaki et al., “The loss of virulence of histone H1 overexpressing Leishmania donovani parasites is directly associated with a reduction of HSP83 rate of translation,” Molecular Microbiology, vol. 88, no. 5, pp. 1015–1031, 2013. View at Publisher · View at Google Scholar · View at Scopus
  168. F. Chappuis, S. Sundar, A. Hailu et al., “Visceral leishmaniasis: what are the needs for diagnosis, treatment and control?” Nature Reviews Microbiology, vol. 5, no. 11, pp. 873–882, 2007. View at Publisher · View at Google Scholar · View at Scopus
  169. M.-C. Brotherton, S. Bourassa, D. Légaré, G. G. Poirier, A. Droit, and M. Ouellette, “Quantitative proteomic analysis of amphotericin B resistance in Leishmania infantum,” International Journal for Parasitology: Drugs and Drug Resistance, vol. 4, no. 2, pp. 126–132, 2014. View at Publisher · View at Google Scholar · View at Scopus
  170. J. Drummelsmith, I. Girard, N. Trudel, and M. Ouellette, “Differential protein expression analysis of Leishmania major reveals novel roles for methionine adenosyltransferase and S-adenosylmethionine in methotrexate resistance,” Journal of Biological Chemistry, vol. 279, no. 32, pp. 33273–33280, 2004. View at Publisher · View at Google Scholar · View at Scopus
  171. P. Kumar, R. Lodge, F. Raymond et al., “Gene expression modulation and the molecular mechanisms involved in Nelfinavir resistance in Leishmania donovani axenic amastigotes,” Molecular Microbiology, vol. 89, no. 3, pp. 565–582, 2013. View at Publisher · View at Google Scholar · View at Scopus
  172. N. Trudel, R. Garg, N. Messier, S. Sundar, M. Ouellette, and M. J. Tremblay, “Intracellular survival of Leishmania species that cause visceral Leishmaniasis is significantly reduced by HIV-1 protease inhibitors,” Journal of Infectious Diseases, vol. 198, no. 9, pp. 1292–1299, 2008. View at Publisher · View at Google Scholar · View at Scopus