Leishmania major strain Friedlin


Alias: Leishmania major MHOM/IL/81/Friedlin, LmjF

Top Publications

  1. Sádlová J, Price H, Smith B, Votýpka J, Volf P, Smith D. The stage-regulated HASPB and SHERP proteins are essential for differentiation of the protozoan parasite Leishmania major in its sand fly vector, Phlebotomus papatasi. Cell Microbiol. 2010;12:1765-79 pubmed publisher
    ..Complementation with HASPB or SHERP alone suggests that HASPB is the dominant effector molecule in this process. ..
  2. Williams R, Smith T, Cull B, Mottram J, Coombs G. ATG5 is essential for ATG8-dependent autophagy and mitochondrial homeostasis in Leishmania major. PLoS Pathog. 2012;8:e1002695 pubmed publisher
    ..The overall result of this is reduced virulence. ..
  3. Williams R, Westrop G, Coombs G. Two pathways for cysteine biosynthesis in Leishmania major. Biochem J. 2009;420:451-62 pubmed publisher
    ..The absence of CS from mammals and the clear differences between CBS of mammals and Leishmania suggest that each of the parasite enzymes could be a viable drug target...
  4. Nunes V, Damasceno J, Freire R, Tosi L. The Hus1 homologue of Leishmania major encodes a nuclear protein that participates in DNA damage response. Mol Biochem Parasitol. 2011;177:65-9 pubmed publisher
    ..Overexpression of LmHus1 confers resistance to the genotoxic drugs hydroxyurea (HU) and methyl methanesulfonate (MMS) and resistance to HU correlates to reduced net DNA damage upon LmHus1 expression. ..
  5. Roy G, Ouellette M. Inactivation of the cytosolic and mitochondrial serine hydroxymethyl transferase genes in Leishmania major. Mol Biochem Parasitol. 2015;204:106-110 pubmed publisher
    ..Overall this work has shown that SHMT is dispensable for Leishmania growth but it may be necessary when growing in environments poor in serine. ..
  6. Dacher M, Morales M, Pescher P, Leclercq O, Rachidi N, Prina E, et al. Probing druggability and biological function of essential proteins in Leishmania combining facilitated null mutant and plasmid shuffle analyses. Mol Microbiol. 2014;93:146-66 pubmed publisher
    ..The approaches presented here are broadly applicable to any essential gene in Leishmania thus overcoming major bottlenecks for their functional genetic analysis and their exploitation for structure-informed drug development. ..
  7. Moen S, Fairman J, Barnes S, Sullivan A, Nakazawa Hewitt S, Van Voorhis W, et al. Structures of prostaglandin F synthase from the protozoa Leishmania major and Trypanosoma cruzi with NADP. Acta Crystallogr F Struct Biol Commun. 2015;71:609-14 pubmed publisher
    ..major PGF with NADP. These structures were determined by molecular replacement to a final R factor of less than 18.6% (Rfree of less than 22.9%). PGF in the infectious protozoa L. major and T. cruzi is a potential therapeutic target. ..
  8. Fyfe P, Westrop G, Ramos T, Muller S, Coombs G, Hunter W. Structure of Leishmania major cysteine synthase. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012;68:738-43 pubmed publisher
    ..The structure surprisingly revealed that the cofactor pyridoxal phosphate had been lost during crystallization. ..
  9. Williams R, Mottram J, Coombs G. Distinct roles in autophagy and importance in infectivity of the two ATG4 cysteine peptidases of Leishmania major. J Biol Chem. 2013;288:3678-90 pubmed publisher
    ..2 appears to be the more important. Moreover, the low infectivity of ?atg4.2 demonstrates that autophagy is important for the virulence of the parasite. ..

More Information


  1. Tonoli C, Vieira P, Ward R, Arni R, de Oliveira A, Murakami M. Production, purification, crystallization and preliminary X-ray diffraction studies of the nucleoside diphosphate kinase b from Leishmania major. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009;65:1116-9 pubmed publisher
    ..2 angstrom resolution and belonged to the trigonal crystal system, with unit-cell parameters a = 114.2, c = 93.9 angstrom. Translation-function calculations yielded an unambiguous solution in the enantiomorphic space group P3(2)21. ..
  2. Faím L, Rosa e Silva I, Bertacine Dias M, d Muniz Pereira H, Brandao Neto J, Alves da Silva M, et al. Crystallization and preliminary X-ray diffraction analysis of selenophosphate synthetases from Trypanosoma brucei and Leishmania major. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013;69:864-7 pubmed publisher
    ..The Trypanosoma brucei SPS orthologue (TbSPS2) was crystallized by the microbatch method using paraffin oil. X-ray diffraction data were collected to resolutions of 1.9 Å for ?N-LmSPS2 and 3.4 Å for TbSPS2. ..
  3. Eadsforth T, Cameron S, Hunter W. The crystal structure of Leishmania major N(5),N(10)-methylenetetrahydrofolate dehydrogenase/cyclohydrolase and assessment of a potential drug target. Mol Biochem Parasitol. 2012;181:178-85 pubmed publisher
    ..Additionally, residues that interact and participate in catalysis in the human homologue are conserved amongst trypanosomatid sequences and this may complicate attempts to derive potent, parasite specific DHCH inhibitors. ..
  4. Heng J, Saunders E, Gooley P, McConville M, Naderer T, Tull D. Membrane targeting of the small myristoylated protein 2 (SMP-2) in Leishmania major. Mol Biochem Parasitol. 2013;190:1-5 pubmed publisher
    ..Thus while the core sequences of the SMPs are highly conserved, individual members have evolved different mechanisms for their diverse membrane localization. ..
  5. Manzano J, Perea A, León Guerrero D, Campos Salinas J, Piacenza L, Castanys S, et al. Leishmania LABCG1 and LABCG2 transporters are involved in virulence and oxidative stress: functional linkage with autophagy. Parasit Vectors. 2017;10:267 pubmed publisher
    ..The overall conclusion is that LABCG1-2 transporters could play a key role in Leishmania cell survival and infectivity. ..
  6. Singh K, Veluru N, Trivedi V, Gupta C, Sahasrabuddhe A. An actin-like protein is involved in regulation of mitochondrial and flagellar functions as well as in intramacrophage survival of Leishmania donovani. Mol Microbiol. 2014;91:562-78 pubmed publisher
    ..Here, we show that a novel actin-related protein (ORF LmjF.13.0950) is localized mainly in the Leishmania mitochondrion...
  7. Campelo R, Díaz Lozano I, Figarella K, Osuna A, Ramírez J. Leishmania major telomerase TERT protein has a nuclear/mitochondrial eclipsed distribution that is affected by oxidative stress. Infect Immun. 2015;83:57-66 pubmed publisher
    ..Finally, overexpression of TERT in Leishmania transfected cells not only increased the parasitic cell growth rate but also increased their resistance to oxidative stress. ..
  8. Vieira P, de Jesus Santos A, De Oliveira A. Biophysical Characterization of the Nucleoside Diphosphate Kinase of Leishmania major and Effect of the P95S Mutation. Protein Pept Lett. 2016;23:99-106 pubmed
  9. Doehl J, Sadlova J, Aslan H, Pruzinova K, Metangmo S, Votypka J, et al. Leishmania HASP and SHERP Genes Are Required for In Vivo Differentiation, Parasite Transmission and Virulence Attenuation in the Host. PLoS Pathog. 2017;13:e1006130 pubmed publisher
    ..This HASPA2-dependent effect is reversed by HASPA1 gene addition, suggesting that the HASPAs may have a role in host immunomodulation. ..
  10. Taheri T, Salmanian A, Gholami E, Doustdari F, Zahedifard F, Rafati S. Leishmania major: disruption of signal peptidase type I and its consequences on survival, growth and infectivity. Exp Parasitol. 2010;126:135-45 pubmed publisher
    ..g. in differentiation and survival of amastigotes. Apparently, the SPase I expression is not essential for in vitro growth of the parasite. ..
  11. Caserta S, Kleczkowska J, Mondino A, Zamoyska R. Reduced functional avidity promotes central and effector memory CD4 T cell responses to tumor-associated antigens. J Immunol. 2010;185:6545-54 pubmed publisher
    ..Our data indicate that, in situations of persistent Ag challenge, generating T cells with reduced functional avidity may elicit more effective immune responses...
  12. Contreras I, G mez M, Nguyen O, Shio M, McMaster R, Olivier M. Leishmania-induced inactivation of the macrophage transcription factor AP-1 is mediated by the parasite metalloprotease GP63. PLoS Pathog. 2010;6:e1001148 pubmed publisher
    ..Together our results indicate a novel role of the surface protease GP63 in the Leishmania-mediated subversion of host AP-1 activity...
  13. C ceres A, Qui ones W, Gualdr n M, Cordeiro A, Avil n L, Michels P, et al. Molecular and biochemical characterization of novel glucokinases from Trypanosoma cruzi and Leishmania spp. Mol Biochem Parasitol. 2007;156:235-45 pubmed publisher
  14. Waller J, Alvarez S, Naponelli V, Lara Nu ez A, Blaby I, Da Silva V, et al. A role for tetrahydrofolates in the metabolism of iron-sulfur clusters in all domains of life. Proc Natl Acad Sci U S A. 2010;107:10412-7 pubmed publisher
    ..Thus COG0354 proteins have an ancient, conserved, folate-dependent function in the activity of certain Fe/S cluster enzymes...
  15. Tammana T, Sahasrabuddhe A, Bajpai V, Gupta C. ADF/cofilin-driven actin dynamics in early events of Leishmania cell division. J Cell Sci. 2010;123:1894-901 pubmed publisher
    ..All these abnormalities are, however, reversed by episomal complementation. Together, these results indicate that actin dynamics regulates early events in Leishmania cell division...
  16. Scott D, Hickerson S, Vickers T, Beverley S. The role of the mitochondrial glycine cleavage complex in the metabolism and virulence of the protozoan parasite Leishmania major. J Biol Chem. 2008;283:155-65 pubmed publisher
    ..Notably, genome-based predictions suggest the related parasite Trypanosoma brucei is totally dependent on the GCC for 5,10-CH(2)-THF synthesis...
  17. Perteguer M, G mez Puertas P, Ca avate C, Dagger F, G rate T, Valdivieso E. Ddi1-like protein from Leishmania major is an active aspartyl proteinase. Cell Stress Chaperones. 2013;18:171-81 pubmed publisher
    ..Our results indicate that the isolated Ddi1-like protein is a functional aspartyl proteinase in L. major, opening possibility to be considered as a potential target for novel antiparasitic drugs...
  18. Martínez García M, Campos Salinas J, Cabello Donayre M, Pineda Molina E, Gálvez F, Orrego L, et al. LmABCB3, an atypical mitochondrial ABC transporter essential for Leishmania major virulence, acts in heme and cytosolic iron/sulfur clusters biogenesis. Parasit Vectors. 2016;9:7 pubmed publisher
    ..Hence, LmABCB3 could represent a novel target to combat leishmaniasis. ..
  19. Kamir D, Zierow S, Leng L, Cho Y, Diaz Y, Griffith J, et al. A Leishmania ortholog of macrophage migration inhibitory factor modulates host macrophage responses. J Immunol. 2008;180:8250-61 pubmed
    ..The ability of Lm1740MIF to inhibit apoptosis may facilitate the persistence of Leishmania within the macrophage and contribute to its evasion from immune destruction...
  20. Norris Mullins B, Vanderkolk K, Vacchina P, Joyce M, Morales M. LmaPA2G4, a homolog of human Ebp1, is an essential gene and inhibits cell proliferation in L. major. PLoS Negl Trop Dis. 2014;8:e2646 pubmed publisher
    ..In conclusion, LmaPA2G4 is an essential gene and is potentially implicated in fundamental biological mechanisms, such as translation, making it an attractive target for therapeutic intervention...
  21. Vidal A, Harkiolaki M, Gallego C, Castillo Acosta V, Ruiz P rez L, Wilson K, et al. Crystal structure and DNA repair activities of the AP endonuclease from Leishmania major. J Mol Biol. 2007;373:827-38 pubmed publisher
  22. Gannavaram S, Vedvyas C, Debrabant A. Conservation of the pro-apoptotic nuclease activity of endonuclease G in unicellular trypanosomatid parasites. J Cell Sci. 2008;121:99-109 pubmed publisher
  23. Isaza C, Zhong X, Rosas L, White J, Chen R, Liang G, et al. A proposed role for Leishmania major carboxypeptidase in peptide catabolism. Biochem Biophys Res Commun. 2008;373:25-9 pubmed publisher
    ..major life cycle. These studies reveal that LmaCP1 expression occurs only in procyclic promastigotes--the stage of life where the organism resides in the abdominal midgut of the insect. The implications of these results are discussed...
  24. Tammana T, Sahasrabuddhe A, Mitra K, Bajpai V, Gupta C. Actin-depolymerizing factor, ADF/cofilin, is essentially required in assembly of Leishmania flagellum. Mol Microbiol. 2008;70:837-52 pubmed publisher
    ..These results for the first time indicate that the actin dynamics-regulating protein ADF/cofilin plays a critical role in assembly and motility of the eukaryotic flagellum...
  25. Richardson J, Morrison L, Bland N, Bruce S, Coombs G, Mottram J, et al. Structures of Leishmania major orthologues of macrophage migration inhibitory factor. Biochem Biophys Res Commun. 2009;380:442-8 pubmed publisher
    ..Analysis of the Leishmania braziliensis genome showed that this species lacks both MIF genes. Thus MIF is not a virulence factor in all species of Leishmania...
  26. Price H, Paape D, Hodgkinson M, Farrant K, Doehl J, Stark M, et al. The Leishmania major?BBSome subunit BBS1 is essential for parasite virulence in the mammalian host. Mol Microbiol. 2013;90:597-611 pubmed publisher
    ..This is the first report of an association between the BBSome complex and pathogen infectivity...
  27. Nare B, Garraway L, Vickers T, Beverley S. PTR1-dependent synthesis of tetrahydrobiopterin contributes to oxidant susceptibility in the trypanosomatid protozoan parasite Leishmania major. Curr Genet. 2009;55:287-99 pubmed publisher
    ..Since the intracellular pteridine levels of Leishmania can be readily manipulated, these organisms offer a powerful setting for the dissection of pteridine-dependent oxidant susceptibility in higher eukaryotes...
  28. Marciano D, Maugeri D, Cazzulo J, Nowicki C. Functional characterization of stage-specific aminotransferases from trypanosomatids. Mol Biochem Parasitol. 2009;166:172-82 pubmed publisher
    ..ALATs are expressed in the clinically important stages of TriTryps, probably fulfilling an essential role, which deserves further studies...
  29. Horjales S, Schmidt Arras D, Limardo R, Leclercq O, Obal G, Prina E, et al. The crystal structure of the MAP kinase LmaMPK10 from Leishmania major reveals parasite-specific features and regulatory mechanisms. Structure. 2012;20:1649-60 pubmed publisher
    ..Overall, these data should speed the discovery of molecules interfering with LmaMPK10 functions, with relevance for antileishmanial drug development strategies...
  30. Munday J, McLuskey K, Brown E, Coombs G, Mottram J. Oligopeptidase B deficient mutants of Leishmania major. Mol Biochem Parasitol. 2011;175:49-57 pubmed publisher
    ..major OPB. This suggested that the residues involved in the S1 and S2 subsites of OPB2 are identical to OPB and hence the substrate specificity would be similar. Consequently there may be redundancy between the two enzymes...
  31. McLuskey K, Paterson N, Bland N, Isaacs N, Mottram J. Crystal structure of Leishmania major oligopeptidase B gives insight into the enzymatic properties of a trypanosomatid virulence factor. J Biol Chem. 2010;285:39249-59 pubmed publisher
    ..It could facilitate the development of specific OPB inhibitors with therapeutic potential by exploiting its unique substrate recognition properties as well as providing a model for OPBs in general...
  32. Feliciano P, Drennan C, Nonato M. Crystal structure of an Fe-S cluster-containing fumarate hydratase enzyme from Leishmania major reveals a unique protein fold. Proc Natl Acad Sci U S A. 2016;113:9804-9 pubmed publisher
    ..Taken together, these data provide a framework both for investigations of the class I FH catalytic mechanism and for drug design aimed at fighting neglected tropical diseases. ..