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J-binding protein 1 and J-binding protein 2 expression in clinical Leishmania major no response-antimonial isolates

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Abstract

Cutaneous leishmaniasis (CL) is a major disease in many parts of the world. Since no vaccine has been developed, treatment is the best way to control it. In most areas, antimonial resistance whose mechanisms have not been completely understood has been reported. The main aim of this study is gene expression assessing of J-binging protein 1 and J-binding protein 2 in clinical Leishmania major isolates. The patients with CL from central and north Iran were considered for this study. The samples were transferred in RNAlater solution and stored in − 20 °C. RNA extraction and cDNA synthesis were performed. The gene expression analysis was done with SYBR Green real-time PCR using ∆∆CT. Written informed consent forms were filled out by patients, and then, information forms were filled out based on the Helsinki Declaration. Statistical analysis was done with SPSS (16.0; SPSS Inc, Chicago) using independent t test, Shapiro–Wilk, and Pearson’s and Spearman’s rank correlation coefficients. P ≤ 0.05 was considered significant. The gene expression of JBP1 and JBP2 had no relation with sex and age. The JBP1 gene expression was high in sensitive isolates obtained from north of the country. The JBP2 gene expression was significant in sensitive and no response-antimonial isolates from the north, but no significant differences were detected in sensitive and resistant isolates from central Iran. Differential gene expression of JBP1 and JBP2 in various clinical resistances isolates in different geographical areas shows multifactorial ways of developing resistance in different isolates.

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Abbreviations

CL:

Cutaneous leishmaniasis (CL)

ACL:

Anthroponotic cutaneous leishmaniasis

ZCL:

Zoonotic cutaneous leishmaniasis

JBP:

J-binding protein

RNAP II:

RNA polymerase II

ITS:

Internal transcribed spacer

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

References

  • Adaui V, Schnorbusch K, Zimic M, Gutiérrez A, Decuypere S, Vanaerschot M et al (2011) Comparison of gene expression patterns among Leishmania braziliensis clinical isolates showing a different in vitro susceptibility to pentavalent antimony. Parasitology 138:183–193

    Article  CAS  PubMed  Google Scholar 

  • Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W et al (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Altschul SF, Wootton JC, Gertz EM, Agarwala R, Morgulis A, Schäffer AA et al (2005) Protein database searches using compositionally adjusted substitution matrices. FEBS J 272:5101–5109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Borst P, Sabatini R (2008) Base J: discovery, biosynthesis, and possible functions. Annu Rev Microbiol 62:235–251

    Article  CAS  PubMed  Google Scholar 

  • Brochu C, Haimeur A, Ouellette M (2004) The heat shock protein HSP70 and heat shock cognate protein HSC70 contribute to antimony tolerance in the protozoan parasite Leishmania. Cell Stress Chaperones 9:294–303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Campbell DA, Thomas S, Sturm N (2003) Transcription in kinetoplastid protozoa: why be normal? Microbes Infect 5:1231–1240

    Article  CAS  PubMed  Google Scholar 

  • Choudhury K, Zander D, Kube M, Reinhardt R, Clos J (2008) Identification of a Leishmania infantum gene mediating resistance to miltefosine and SbIII. Int J Parasitol 38:1411–1423

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cliffe LJ, Kieft R, Southern T, Birkeland SR, Marshall M, Sweeney K et al (2009) JBP1 and JBP2 are two distinct thymidine hydroxylases involved in J biosynthesis in genomic DNA of African trypanosomes. Nucleic Acids Res 37:1452–1462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Decuypere S, Rijal S, Yardley V, De Doncker S, Laurent T, Khanal B et al (2005) Gene expression analysis of the mechanism of natural Sb (V) resistance in Leishmania donovani isolates from Nepal. Antimicrob Agents Chemother 49:4616–4621

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • DiPaolo C, Kieft R, Cross M, Sabatini R (2005) Regulation of trypanosome DNA glycosylation by a SWI2/SNF2-like protein. Mol Cell 17:441–451

    Article  CAS  PubMed  Google Scholar 

  • Downing T, Imamura H, Decuypere S, Clark TG, Coombs GH, Cotton JA et al (2011) Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance. Genome Res 21:2143–2156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ekanayake DK, Sabatini R (2011) Epigenetic regulation of polymerase II transcription initiation in Trypanosoma cruzi: modulation of nucleosome abundance, histone modification, and polymerase occupancy by O-linked thymine DNA glucosylation. Eukaryot Cell 10:1465–1472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eslami G, Salehi R (2014) Genetic variation in RPOIILS gene encoding RNA polymerase II largest subunit from Leishmania major. Mol Biol Rep 41:2585–2589

    Article  CAS  PubMed  Google Scholar 

  • Eslami G, Frikha F, Salehi R, Khamesipour A, Hejazi H, Nilforoushzadeh MA (2011) Cloning, expression and dynamic simulation of TRYP6 from Leishmania major (MRHO/IR/75/ER). Mol Biol Rep 38:3765–3776

    Article  CAS  PubMed  Google Scholar 

  • Eslami G, Salehi R, Khosravi S, Doudi M (2012) Genetic analysis of clinical isolates of Leishmania major from Isfahan, Iran. J Vector Borne Dis 49:168–174

    CAS  PubMed  Google Scholar 

  • Eslami G, Hajimohammadi B, Jafari AA, Mirzaei F, Gholamrezai M, Anvari H et al (2014) Molecular identification of Leishmania tropica infections in patients with cutaneous leishmaniasis from an endemic central of Iran. Trop Biomed 31:592–599

    PubMed  Google Scholar 

  • Eslami G, Zarchi MV, Moradi A, Hejazi SH, Sohrevardi SM, Vakili M et al (2016) Aquaglyceroporin1 gene expression in antimony resistance and susceptible Leishmania major isolates. J Vector Borne Dis 53:370–374

    CAS  PubMed  Google Scholar 

  • Genest PA, ter Riet B, Dumas C, Papadopoulou B, van Luenen HGAM, Borst P (2005) Formation of linear inverted repeat amplicons following targeting of an essential gene in Leishmania. Nucleic Acids Res 33:1699–1709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Genest PA, Ter Riet B, Cijsouw T, van Luenen HG, Borst P (2007) Telomeric localization of the modified DNA base J in the genome of the protozoan parasite Leishmania. Nucleic Acids Res 35:2116–2124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gommers-Ampt JH, Van Leeuwen F, de Beer AL, Vliegenthart JF, Dizdaroglu M, Kowalak JA et al (1993) Beta-D-glucosyl-hydroxymethyluracil: a novel modified base present in the DNA of the parasitic protozoan T. brucei. Cell 75:1129–1136

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Guerin PJ, Olliaro P, Sundar S, Boelaert M, Croft SL, Desjeux P et al (2002) Visceral leishmaniasis: current status of control, diagnosis, and treatment, and a proposed research and development agenda. Lancet Infect Dis 2:494–501

    Article  PubMed  Google Scholar 

  • Hazelbaker DZ, Buratowski S (2012) Base J: blocking RNA polymerase’s way. Curr Biol 22:R960–R962

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herwaldt BL (1999) Leishmaniasis. Lancet 354:1191–1199

    Article  CAS  PubMed  Google Scholar 

  • Iyer LM, Tahiliani M, Rao A, Aravind L (2009) Prediction of novel families of enzymes involved in oxidative and other complex modifications of bases in nucleic acids. Cell Cycle 8:1698–1710

    Article  CAS  PubMed  Google Scholar 

  • Jeddi F, Mary C, Aoun K, Harrat Z, Bouratbine A, Faraut F et al (2014) Heterogeneity of molecular resistance patterns in antimony-resistant field isolates of Leishmania species from the Western Mediterranean area. Antimicrob Agents Chemother 58:4866–4874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kazemi-Rad E, Mohebali M, Khadem-Erfan MB, Saffari M, Raoofian R, Hajjaran H et al (2013) Identification of antimony resistance markers in Leishmania tropica field isolates through a cDNA-AFLP approach. Exp Parasitol 35:344–349

    Article  CAS  Google Scholar 

  • Kramer S (2012) Developmental regulation of gene expression in the absence of transcriptional control: the case of kinetoplastids. Mol Biochem Parasitol 181:61–72

    Article  CAS  PubMed  Google Scholar 

  • Kumar D, Singh R, Bhandari V, Kulshrestha A, Negi NS, Salotra P (2012) Biomarkers of antimony resistance: need for expression analysis of multiple genes to distinguish resistance phenotype in clinical isolates of Leishmania donovani. Parasitol Res 111:223–230

    Article  PubMed  Google Scholar 

  • Lee TI, Young RA (2000) Transcription of eukaryotic protein-coding genes. Annu Rev Genet 34:77–137

    Article  CAS  PubMed  Google Scholar 

  • Legare D, Cayer S, Singh AK, Richard D, Papadopoulou B, Ouellette M (2001) ABC proteins of Leishmania. J Bioenerg Biomembr 33:469–474

    Article  CAS  PubMed  Google Scholar 

  • Mandal S, Maharjan M, Singh S, Chatterjee M, Madhubala R (2010) Assessing aquaglyceroporin gene status and expression profile in antimony-susceptible and-resistant clinical isolates of Leishmania donovani from India. J Antimicrob Chemother 65:496–507

    Article  CAS  PubMed  Google Scholar 

  • Marquis N, Gourbal B, Rosen BP, Mukhopadhyay R, Ouellette M (2005) Modulation in aquaglyceroporin AQP1 gene transcript levels in drug-resistant Leishmania. Mol Microbiol 57:1690–1699

    Article  CAS  PubMed  Google Scholar 

  • Martinez-Calvillo S, Yan S, Nguyen D, Fox M, Stuart KD, Myler PJ (2003) Transcription of Leishmania major Friedlin chromosome 1 initiates in both directions within a single region. Mol Cell 11:1291–1299

    Article  CAS  PubMed  Google Scholar 

  • Mukherjee A, Padmanabhan PK, Singh S, Roy G, Girard I, Chatterjee M et al (2007) Role of ABC transporter MRPA, γ-glutamylcysteine synthetase and ornithine decarboxylase in natural antimony-resistant isolates of Leishmania donovani. J Antimicrob Chemother 59:204–211

    Article  CAS  PubMed  Google Scholar 

  • Mukherjee A, Boisvert S, Monte-Neto RL, Coelho AC, Raymond F, Mukhopadhyay R et al (2013) Telomeric gene deletion and intrachromosomal amplification in antimony-resistant Leishmania. Mol Microbiol 88:189–202

    Article  CAS  PubMed  Google Scholar 

  • Nühs A, Schäfer C, Zander D, Trübe L, Nevado PT, Schmidt S et al (2014) A novel marker, ARM58, confers antimony resistance to Leishmania spp. Int J Parasitol Drugs Drug Resist 4:37–47

    Article  PubMed  Google Scholar 

  • Paule MR, White RJ (2000) Survey and summary: transcription by RNA polymerases I and III. Nucleic Acids Res 28:1283–1298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y et al (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324:930–935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ubeda JM, Legare D, Raymond F, Ouameur AA, Boisvert S, Rigault P et al (2008) Modulation of gene expression in drug resistant Leishmania is associated with gene amplification, gene deletion and chromosome aneuploidy. Genome Biol 9:R115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van Luenen HG, Farris C, Jan S, Genest PA, Tripathi P, Velds A et al (2012) Glucosylated hydroxymethyluracil, DNA base J, prevents transcriptional readthrough in leishmania. Cell 150:909–921

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vergnes B, Gourbal B, Girard I, Sundar S, Drummelsmith J, Ouellette M (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

    Article  CAS  PubMed  Google Scholar 

  • Yaghoobi-Ershadi MR, Jafari R, Hanafi-Bojd AA (2004) A new epidemic focus of zoonotic cutaneous leishmaniasis in central Iran. Ann Saudi Med 24:98–101

    Article  PubMed  PubMed Central  Google Scholar 

  • Yu Z, Genest PA, ter Riet B, Sweeney K, DiPaolo C, Kieft R et al (2007) The protein that binds to DNA base J in trypanosomatids has features of a thymidine hydroxylase. Nucleic Acids Res 35:2107–2115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to thank the technical support from Research Center for Food Hygiene and Safety, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. This research was financially supported by Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

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Authors and Affiliations

  1. Research Center for Food Hygiene and Safety, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Salman Ahmadian, Gilda Eslami, Saeede Sadat Hosseini & Vahid Ajamein Fahadan

  2. Department of Parasitology and Mycology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Salman Ahmadian, Gilda Eslami, Ali Fatahi & Vahid Ajamein Fahadan

  3. Department of Community and Preventive Medicine, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Mahmoud Vakili

  4. Laboratory of Technologies of Information and Communication and Electrical Engineering (LaTICE), University of Tunis, Tunis, Tunisia

    Mourad Elloumi

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  1. Salman Ahmadian
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  2. Gilda Eslami
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  4. Saeede Sadat Hosseini
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Contributions

GE conceived, designed, and drafted this manuscript. MV performed the statistical analysis. VA obtained the samples. AF drafted the manuscript. SSH and SA performed the laboratory techniques and quality control. ME reviewed the manuscript. All authors read and approved the final manuscript.

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Correspondence to Gilda Eslami.

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Ahmadian, S., Eslami, G., Fatahi, A. et al. J-binding protein 1 and J-binding protein 2 expression in clinical Leishmania major no response-antimonial isolates. J Parasit Dis 43, 39–45 (2019). https://doi.org/10.1007/s12639-018-1052-5

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  • DOI: https://doi.org/10.1007/s12639-018-1052-5

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