1887

Microbial Genomics logo

Volume 6, Issue 9

Dual transcriptome analysis reveals differential gene expression modulation influenced by arginase and host genetic background Open Access

Abstract

The outcome of infection is strongly influenced by the host’s genetic background. BALB/c mice are susceptible to infection, while C57BL/6 mice show discrete resistance. Central to the fate of the infection is the availability of -arginine and the related metabolic processes in the host and parasite. Depending on -arginine availability, nitric oxide synthase 2 (NOS2) of the host cell produces nitric oxide (NO) controlling the parasite growth. On the other hand, can also use host -arginine for the production of polyamines through its own arginase activity, thus favouring parasite replication. Considering RNA-seq data, we analysed the dual modulation of host and parasite gene expression of BALB/c or C57BL/6 mouse bone marrow-derived macrophages (BMDMs) after 4 h of infection with wild-type (-WT) or arginase knockout (-arg). We identified 12 641 host transcripts and 8282 parasite transcripts by alignment analysis with the respective and genomes. The comparison of BALB/c_-arg BALB/c_-WT revealed 233 modulated transcripts, with most related to the immune response and some related to the amino acid transporters and -arginine metabolism. In contrast, the comparison of C57BL/6_-arg C57BL/6_-WT revealed only 30 modulated transcripts, including some related to the immune response but none related to amino acid transport or -arginine metabolism. The transcriptome profiles of the intracellular amastigote revealed 94 modulated transcripts in the comparison of -arg_BALB/c -WT_BALB/c and 45 modulated transcripts in the comparison of -arg_C57BL/6 -WT_C57BL/6. Taken together, our data present new insights into the impact of parasite arginase activity on the orchestration of the host gene expression modulation, including in the immune response and amino acid transport and metabolism, mainly in susceptible BALB/c-infected macrophages. Moreover, we show how parasite arginase activity affects parasite gene expression modulation, including amino acid uptake and amastin expression.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): arginine transport , BALB/c , C57BL/6 , immune response , Leishmania amazonensis , macrophage infection and RNA-seq
Funding
This study was supported by the:
  • Universitetet i Bergen
    • Principle Award Recipient: Audun Helge Nerland
  • Universitetet i Bergen
    • Principle Award Recipient: Karl Erik Müller
  • Senter for Internasjonalisering av Utdanning
    • Principle Award Recipient: Audun Helge Nerland
  • Senter for Internasjonalisering av Utdanning
    • Principle Award Recipient: Karl Erik Müller
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
    • Principle Award Recipient: Juliana ide Aoki
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (Award 308667/2018-2)
    • Principle Award Recipient: Lucile Maria Floeter-Winter
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (Award 406351/2018-0)
    • Principle Award Recipient: Sandra Marcia Muxel
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (Award #2018/23512-0 and #2014/50717-1)
    • Principle Award Recipient: Lucile Maria Floeter-Winter
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (Award #2017/23933-3)
    • Principle Award Recipient: Maria Fernanda Laranjeira-Silva
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (Award #2018/24693-9)
    • Principle Award Recipient: Sandra Marcia Muxel
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (BR) (Award #2016/03273-6)
    • Principle Award Recipient: Juliana ide Aoki
© 2020 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000427
2020-09-04
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/mgen/6/9/mgen000427.html?itemId=/content/journal/mgen/10.1099/mgen.0.000427&mimeType=html&fmt=ahah

References

  1. Burza S, Croft SL, Boelaert M. Leishmaniasis. Lancet 2018; 392:951–970 [View Article][PubMed]
     [Google Scholar]
  2. Muxel SM, Aoki JI, Fernandes JCR, Laranjeira-Silva MF, Zampieri RA et al. Arginine and polyamines fate in Leishmania Infection. Front Microbiol 2017; 8:2682 [View Article][PubMed]
     [Google Scholar]
  3. von Stebut E, Udey MC. Requirements for Th1-dependent immunity against infection with Leishmania major. Microbes Infect 2004; 6:1102–1109 [View Article][PubMed]
     [Google Scholar]
  4. Von Stebut E, Ehrchen JM, Belkaid Y, Kostka SL, Molle K et al. Interleukin 1alpha promotes Th1 differentiation and inhibits disease progression in Leishmania major-susceptible BALB/c mice. J Exp Med 2003; 198:191–199 [View Article][PubMed]
     [Google Scholar]
  5. Alexander J, Brombacher F. T helper1/t helper2 cells and resistance/susceptibility to Leishmania infection: is this paradigm still relevant?. Front Immunol 2012; 3:80 [View Article][PubMed]
     [Google Scholar]
  6. Velasquez LG, Galuppo MK, DE Rezende E, Brandão WN, Peron JP et al. Distinct courses of infection with Leishmania (L.) amazonensis are observed in BALB/c, BALB/c nude and C57BL/6 mice. Parasitology 2016; 143:692–703 [View Article][PubMed]
     [Google Scholar]
  7. Rosas LE, Keiser T, Barbi J, Satoskar AA, Septer A et al. Genetic background influences immune responses and disease outcome of cutaneous L. mexicana infection in mice. Int Immunol 2005; 17:1347–1357 [View Article][PubMed]
     [Google Scholar]
  8. Probst CM, Silva RA, Menezes JPB, Almeida TF, Gomes IN et al. A comparison of two distinct murine macrophage gene expression profiles in response to Leishmania amazonensis infection. BMC Microbiol 2012; 12:22 [View Article][PubMed]
     [Google Scholar]
  9. Aoki JI, Muxel SM, Zampieri RA, Müller KE, Nerland AH et al. Differential immune response modulation in early Leishmania amazonensis infection of BALB/c and C57BL/6 macrophages based on transcriptome profiles. Sci Rep 2019; 9:19841 [View Article][PubMed]
     [Google Scholar]
  10. Gregory DJ, Olivier M. Subversion of host cell signalling by the protozoan parasite Leishmania . Parasitology 2005; 130 Suppl:S27–S35 [View Article][PubMed]
     [Google Scholar]
  11. Rossi M, Fasel N. How to master the host immune system? Leishmania parasites have the solutions!. Int Immunol 2018; 30:103–111 [View Article][PubMed]
     [Google Scholar]
  12. Bogdan C, Röllinghoff M. The immune response to Leishmania: mechanisms of parasite control and evasion. Int J Parasitol 1998; 28:121–134 [View Article][PubMed]
     [Google Scholar]
  13. McConville MJ, de Souza D, Saunders E, Likic VA, Naderer T. Living in a phagolysosome; metabolism of Leishmania amastigotes . Trends Parasitol 2007; 23:368–375 [View Article][PubMed]
     [Google Scholar]
  14. da Silva MFL, Zampieri RA, Muxel SM, Beverley SM, Floeter-Winter LM. Leishmania amazonensis arginase compartmentalization in the glycosome is important for parasite infectivity. PLoS One 2012; 7:e34022 [View Article]
     [Google Scholar]
  15. Roberts SC, Tancer MJ, Polinsky MR, Gibson KM, Heby O et al. Arginase plays a pivotal role in polyamine precursor metabolism in Leishmania. Characterization of gene deletion mutants. J Biol Chem 2004; 279:23668–23678 [View Article][PubMed]
     [Google Scholar]
  16. Boitz JM, Yates PA, Kline C, Gaur U, Wilson ME et al. Leishmania donovani ornithine decarboxylase is indispensable for parasite survival in the mammalian host. Infect Immun 2009; 77:756–763 [View Article][PubMed]
     [Google Scholar]
  17. Boitz JM, Gilroy CA, Olenyik TD, Paradis D, Perdeh J et al. Arginase is essential for survival of Leishmania donovani promastigotes but not intracellular amastigotes. Infect Immun 2017; 85: [View Article][PubMed]
     [Google Scholar]
  18. Jiang Y, Roberts SC, Jardim A, Carter NS, Shih S et al. Ornithine decarboxylase gene deletion mutants of Leishmania donovani . J Biol Chem 1999; 274:3781–3788 [View Article][PubMed]
     [Google Scholar]
  19. Roberts SC, Jiang Y, Jardim A, Carter NS, Heby O et al. Genetic analysis of spermidine synthase from Leishmania donovani . Mol Biochem Parasitol 2001; 115:217–226 [View Article][PubMed]
     [Google Scholar]
  20. da Silva MFL, Floeter-Winter LM. Arginase in Leishmania . Subcell Biochem 2014; 74:103–117 [View Article][PubMed]
     [Google Scholar]
  21. Aoki JI, Muxel SM, Zampieri RA, Acuña SM, Fernandes JCR et al. L-arginine availability and arginase activity: characterization of amino acid permease 3 in Leishmania amazonensis . PLoS Negl Trop Dis 2017; 11:e0006025 [View Article][PubMed]
     [Google Scholar]
  22. Aoki JI, Laranjeira-Silva MF, Muxel SM, Floeter-Winter LM. The impact of arginase activity on virulence factors of Leishmania amazonensis . Curr Opin Microbiol 2019; 52:110–115 [View Article][PubMed]
     [Google Scholar]
  23. Fernandes MC, Dillon LAL, Belew AT, Bravo HC, Mosser DM et al. Dual transcriptome profiling of Leishmania -infected human macrophages reveals distinct reprogramming signatures. mBio 2016; 7:e00027-16 [View Article][PubMed]
     [Google Scholar]
  24. Dillon LAL, Suresh R, Okrah K, Corrada Bravo H, Mosser DM et al. Simultaneous transcriptional profiling of Leishmania major and its murine macrophage host cell reveals insights into host-pathogen interactions. BMC Genomics 2015; 16:1108 [View Article][PubMed]
     [Google Scholar]
  25. Dillon LAL, Okrah K, Hughitt VK, Suresh R, Li Y et al. Transcriptomic profiling of gene expression and RNA processing during Leishmania major differentiation. Nucleic Acids Res 2015; 43:6799–6813 [View Article][PubMed]
     [Google Scholar]
  26. Christensen SM, Dillon LAL, Carvalho LP, Passos S, Novais FO et al. Meta-transcriptome profiling of the Human-Leishmania braziliensis cutaneous lesion. PLoS Negl Trop Dis 2016; 10:e0004992 [View Article][PubMed]
     [Google Scholar]
  27. Fiebig M, Kelly S, Gluenz E. Comparative life cycle transcriptomics revises Leishmania mexicana genome annotation and links a chromosome duplication with parasitism of vertebrates. PLoS Pathog 2015; 11:e1005186 [View Article][PubMed]
     [Google Scholar]
  28. Aoki JI, Muxel SM, Zampieri RA, Laranjeira-Silva MF, Müller KE et al. RNA-seq transcriptional profiling of Leishmania amazonensis reveals an arginase-dependent gene expression regulation. PLoS Negl Trop Dis 2017; 11:e0006026 [View Article][PubMed]
     [Google Scholar]
  29. Rastrojo A, Carrasco-Ramiro F, Martín D, Crespillo A, Reguera RM et al. The transcriptome of Leishmania major in the axenic promastigote stage: transcript annotation and relative expression levels by RNA-seq. BMC Genomics 2013; 14:223 [View Article][PubMed]
     [Google Scholar]
  30. Rastrojo A, Corvo L, Lombraña R, Solana JC, Aguado B et al. Analysis by RNA-seq of transcriptomic changes elicited by heat shock in Leishmania major. Sci Rep 2019; 9:6919 [View Article][PubMed]
     [Google Scholar]
  31. da Silva MFL, Zampieri RA, Muxel SM, Beverley SM, Floeter-Winter LM. Leishmania amazonensis arginase compartmentalization in the glycosome is important for parasite infectivity. PLoS One 2012; 7:e34022 [View Article][PubMed]
     [Google Scholar]
  32. Muxel SM, Laranjeira-Silva MF, Zampieri RA, Floeter-Winter LM. Leishmania (Leishmania) amazonensis induces macrophage miR-294 and miR-721 expression and modulates infection by targeting NOS2 and L-arginine metabolism. Sci Rep 2017; 7:44141 [View Article][PubMed]
     [Google Scholar]
  33. Aoki JI, Yamashiro-Kanashiro EH, Ramos DCC, Cotrim PC. Efficacy of the tubercidin antileishmania action associated with an inhibitor of the nucleoside transport. Parasitol Res 2009; 104:223–228 [View Article][PubMed]
     [Google Scholar]
  34. do Socorro S Rosa MdoSS, Mendonça-Filho RR, de Almeida Rodrigues I, Soares RMA, Soares RMA et al. Antileishmanial activity of a linalool-rich essential oil from Croton cajucara . Antimicrob Agents Chemother 2003; 47:1895–1901 [View Article][PubMed]
     [Google Scholar]
  35. Van der Auwera GA, Carneiro MO, Hartl C, Poplin R, Del Angel G et al. From FastQ data to high confidence variant calls: the genome analysis toolkit best practices pipeline. Curr Protoc Bioinformatics 2013; 43:0.1–033 [View Article][PubMed]
     [Google Scholar]
  36. Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 2014; 30:2114–2120 [View Article][PubMed]
     [Google Scholar]
  37. Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R et al. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol 2013; 14:R36 [View Article][PubMed]
     [Google Scholar]
  38. Trapnell C, Pachter L, Salzberg SL. TopHat: discovering splice junctions with RNA-seq. Bioinformatics 2009; 25:1105–1111 [View Article][PubMed]
     [Google Scholar]
  39. Trapnell C, Roberts A, Goff L, Pertea G, Kim D et al. Differential gene and transcript expression analysis of RNA-Seq experiments with TopHat and Cufflinks. Nat Protoc 2012; 7:562–578 [View Article][PubMed]
     [Google Scholar]
  40. Mortazavi A, Williams BA, McCue K, Schaeffer L, Wold B. Mapping and quantifying mammalian transcriptomes by RNA-seq. Nat Methods 2008; 5:621–628 [View Article][PubMed]
     [Google Scholar]
  41. Benjamini Y, Drai D, Elmer G, Kafkafi N, Golani I. Controlling the false discovery rate in behavior genetics research. Behav Brain Res 2001; 125:279–284 [View Article][PubMed]
     [Google Scholar]
  42. Warde-Farley D, Donaldson SL, Comes O, Zuberi K, Badrawi R et al. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res 2010; 38:W214–W220 [View Article][PubMed]
     [Google Scholar]
  43. Ji J, Sun J, Qi H, Soong L. Analysis of T helper cell responses during infection with Leishmania amazonensis . Am J Trop Med Hyg 2002; 66:338–345 [View Article][PubMed]
     [Google Scholar]
  44. Ji J, Sun J, Soong L. Impaired expression of inflammatory cytokines and chemokines at early stages of infection with Leishmania amazonensis . Infect Immun 2003; 71:4278–4288 [View Article][PubMed]
     [Google Scholar]
  45. Racoosin EL, Beverley SM. Leishmania major: promastigotes induce expression of a subset of chemokine genes in murine macrophages. Exp Parasitol 1997; 85:283–295 [View Article][PubMed]
     [Google Scholar]
  46. Matte C, Olivier M. Leishmania-induced cellular recruitment during the early inflammatory response: modulation of proinflammatory mediators. J Infect Dis 2002; 185:673–681 [View Article][PubMed]
     [Google Scholar]
  47. Zambrano-Villa S, Rosales-Borjas D, Carrero JC, Ortiz-Ortiz L. How protozoan parasites evade the immune response. Trends Parasitol 2002; 18:272–278 [View Article][PubMed]
     [Google Scholar]
  48. Janeway CA, Medzhitov R. Innate immune recognition. Annu Rev Immunol 2002; 20:197–216 [View Article][PubMed]
     [Google Scholar]
  49. Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature 2007; 449:819–826 [View Article][PubMed]
     [Google Scholar]
  50. Liese J, Schleicher U, Bogdan C. The innate immune response against Leishmania parasites . Immunobiology 2008; 213:377–387 [View Article][PubMed]
     [Google Scholar]
  51. Roach DR, Bean AGD, Demangel C, France MP, Briscoe H et al. TNF regulates chemokine induction essential for cell recruitment, granuloma formation, and clearance of mycobacterial infection. J Immunol 2002; 168:4620–4627 [View Article][PubMed]
     [Google Scholar]
  52. Teixeira MJ, Teixeira CR, Andrade BB, Barral-Netto M, Barral A. Chemokines in host-parasite interactions in leishmaniasis. Trends Parasitol 2006; 22:32–40 [View Article][PubMed]
     [Google Scholar]
  53. Lüder CG, Campos-Salinas J, Gonzalez-Rey E, van Zandbergen G. Impact of protozoan cell death on parasite-host interactions and pathogenesis. Parasit Vectors 2010; 3:116 [View Article][PubMed]
     [Google Scholar]
  54. Bansal V, Ochoa JB. Arginine availability, arginase, and the immune response. Curr Opin Clin Nutr Metab Care 2003; 6:223–228 [View Article][PubMed]
     [Google Scholar]
  55. Hatzoglou M, Fernandez J, Yaman I, Closs E. Regulation of cationic amino acid transport: the story of the CAT-1 transporter. Annu Rev Nutr 2004; 24:377–399 [View Article][PubMed]
     [Google Scholar]
  56. Lopez AB, Wang C, Huang CC, Yaman I, Li Y et al. A feedback transcriptional mechanism controls the level of the arginine/lysine transporter CAT-1 during amino acid starvation. Biochem J 2007; 402:163–173 [View Article][PubMed]
     [Google Scholar]
  57. Muxel SM, Mamani-Huanca M, Aoki JI, Zampieri RA, Floeter-Winter LM et al. Metabolomic profile of BALB/c macrophages infected with Leishmania amazonensis: deciphering L-arginine metabolism. Int J Mol Sci 2019; 20:6248 [View Article][PubMed]
     [Google Scholar]
  58. Castilho-Martins EA, Canuto GA, Muxel SM, da Silva MF, Floeter-Winter LM et al. Capillary electrophoresis reveals polyamine metabolism modulation in Leishmania (Leishmania) amazonensis wild-type and arginase-knockout mutants under arginine starvation. Electrophoresis 2015; 36:2314–2323 [View Article]
     [Google Scholar]
  59. Darlyuk I, Goldman A, Roberts SC, Ullman B, Rentsch D et al. Arginine homeostasis and transport in the human pathogen Leishmania donovani . J Biol Chem 2009; 284:19800–19807 [View Article][PubMed]
     [Google Scholar]
  60. Shaked-Mishan P, Suter-Grotemeyer M, Yoel-Almagor T, Holland N, Zilberstein D et al. A novel high-affinity arginine transporter from the human parasitic protozoan Leishmania donovani. Mol Microbiol 2006; 60:30–38 [View Article][PubMed]
     [Google Scholar]
  61. Castilho-Martins EA, Laranjeira da Silva MF, dos Santos MG, Muxel SM, Floeter-Winter LM. Axenic Leishmania amazonensis promastigotes sense both the external and internal arginine pool distinctly regulating the two transporter-coding genes. PLoS One 2011; 6:e27818 [View Article][PubMed]
     [Google Scholar]
  62. Castilho-Martins EA, Canuto GAB, Muxel SM, daSilva MFL, Floeter-Winter LM et al. Capillary electrophoresis reveals polyamine metabolism modulation in Leishmania (Leishmania) amazonensis wild-type and arginase-knockout mutants under arginine starvation. Electrophoresis 2015; 36:2314–2323 [View Article][PubMed]
     [Google Scholar]
  63. Igarashi K, Kashiwagi K. Characteristics of cellular polyamine transport in prokaryotes and eukaryotes. Plant Physiol Biochem 2010; 48:506–512 [View Article][PubMed]
     [Google Scholar]
  64. Kurihara T, Arimochi H, Bhuyan ZA, Ishifune C, Tsumura H et al. CD98 heavy chain is a potent positive regulator of CD4+ T cell proliferation and interferon-γ production in vivo. PLoS One 2015; 10:e0139692 [View Article][PubMed]
     [Google Scholar]
  65. Lima-Junior DS, Costa DL, Carregaro V, Cunha LD, Silva ALN et al. Inflammasome-derived IL-1β production induces nitric oxide-mediated resistance to Leishmania. Nat Med 2013; 19:909–915 [View Article][PubMed]
     [Google Scholar]
  66. Fernández-Figueroa EA, Rangel-Escareño C, Espinosa-Mateos V, Carrillo-Sánchez K, Salaiza-Suazo N et al. Disease severity in patients infected with Leishmania mexicana relates to IL-1β. PLoS Negl Trop Dis 2012; 6:e1533 [View Article][PubMed]
     [Google Scholar]
  67. Charmoy M, Hurrell BP, Romano A, Lee SH, Ribeiro-Gomes F et al. The Nlrp3 inflammasome, IL-1β, and neutrophil recruitment are required for susceptibility to a nonhealing strain of Leishmania major in C57BL/6 mice. Eur J Immunol 2016; 46:897–911 [View Article][PubMed]
     [Google Scholar]
  68. Ohtsuka M, Inoko H, Kulski JK, Yoshimura S. Major histocompatibility complex (MHC) class Ib gene duplications, organization and expression patterns in mouse strain C57BL/6. BMC Genomics 2008; 9:178 [View Article][PubMed]
     [Google Scholar]
  69. Rogers MB, Hilley JD, Dickens NJ, Wilkes J, Bates PA et al. Chromosome and gene copy number variation allow major structural change between species and strains of Leishmania. Genome Res 2011; 21:2129–2142 [View Article][PubMed]
     [Google Scholar]
  70. Britto C, Ravel C, Bastien P, Blaineau C, Pagès M et al. Conserved linkage groups associated with large-scale chromosomal rearrangements between old world and new world Leishmania genomes. Gene 1998; 222:107–117 [View Article][PubMed]
     [Google Scholar]
  71. Real F, Vidal RO, Carazzolle MF, Mondego JMC, Costa GGL et al. The genome sequence of Leishmania (Leishmania) amazonensis: functional annotation and extended analysis of gene models. DNA Res 2013; 20:567–581 [View Article][PubMed]
     [Google Scholar]
  72. Patino LH, Muskus C, Ramírez JD. Transcriptional responses of Leishmania (Leishmania) amazonensis in the presence of trivalent sodium stibogluconate. Parasit Vectors 2019; 12:348 [View Article][PubMed]
     [Google Scholar]
  73. Jackson AP. The evolution of amastin surface glycoproteins in trypanosomatid parasites. Mol Biol Evol 2010; 27:33–45 [View Article][PubMed]
     [Google Scholar]
  74. Rochette A, Raymond F, Corbeil J, Ouellette M, Papadopoulou B. Whole-genome comparative RNA expression profiling of axenic and intracellular amastigote forms of Leishmania infantum. Mol Biochem Parasitol 2009; 165:32–47 [View Article][PubMed]
     [Google Scholar]
  75. Bartholomeu DC, de Paiva RMC, Mendes TAO, DaRocha WD, Teixeira SMR. Unveiling the intracellular survival gene kit of trypanosomatid parasites. PLoS Pathog 2014; 10:e1004399 [View Article][PubMed]
     [Google Scholar]
  76. Wu Y, El Fakhry Y, Sereno D, Tamar S, Papadopoulou B. A new developmentally regulated gene family in Leishmania amastigotes encoding a homolog of amastin surface proteins. Mol Biochem Parasitol 2000; 110:345–357 [View Article][PubMed]
     [Google Scholar]
  77. Aoki JI, Coelho AC, Muxel SM, Zampieri RA, Sanchez EMR et al. Characterization of a novel endoplasmic reticulum protein involved in tubercidin resistance in Leishmania major. PLoS Negl Trop Dis 2016; 10:e0004972 [View Article][PubMed]
     [Google Scholar]
  78. Laranjeira-Silva MF, Wang W, Samuel TK, Maeda FY, Michailowsky V et al. A MFS-like plasma membrane transporter required for Leishmania virulence protects the parasites from iron toxicity. PLoS Pathog 2018; 14:e1007140 [View Article][PubMed]
     [Google Scholar]
  79. Martins VT, Duarte MC, Chávez-Fumagalli MA, Menezes-Souza D, Coelho CSP et al. A Leishmania-specific hypothetical protein expressed in both promastigote and amastigote stages of Leishmania infantum employed for the serodiagnosis of, and as a vaccine candidate against, visceral leishmaniasis. Parasit Vectors 2015; 8:363 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000427
Loading
Dual transcriptome analysis reveals differential gene expression modulation influenced by Leishmania arginase and host genetic background
M Gen 6, e000427 (2020); https://doi.org/10.1099/mgen.0.000427
/content/journal/mgen/10.1099/mgen.0.000427
/content/journal/mgen/10.1099/mgen.0.000427
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Supplementary material 2

EXCEL

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error