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The effect of griseofulvin on the gene regulation of β-tubulin in the dermatophyte pathogen Trichophyton rubrum

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Journal of Infection and Chemotherapy

Abstract

Griseofulvin – a mold metabolite produced by Penicillium griseofulvum – is an antifungal drug whose interaction with tubulin is poorly understood. In this study we cloned the β-tubulin gene in Trichophyton rubrum, which encodes a polypeptide with 447 amino acids (accession number AAV33733). Nucleotide sequence comparison in data banks for both the partial DNA and its deduced amino acid sequence revealed significant homology with members of the eukaryotic β-tubulin gene family. Investigation based on real-time polymerase chain reaction (PCR) indicated that griseofulvin treatment of T. rubrum fungal cells decreased the expression of the β-tubulin gene in a dose-dependent manner. However, fluconazole had no effect on the β-tubulin transcript level under the same circumstances. The identification of this vital gene, which is potentially involved in many cellular functions in pathogenic dermatophyte fungi, is the first step towards understanding the functional characteristics of β-tubulin in such fungi and may help in the development of new antifungal drugs against dermatophytes.

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References

  1. M Borgers H Degreef G Cauwenbergh (2005) ArticleTitleFungal infections of the skin: infection process and antimycotic therapy Curr Drug Targets 6 849–62 Occurrence Handle16375669 Occurrence Handle10.2174/138945005774912726 Occurrence Handle1:CAS:528:DC%2BD2MXht1Grt73P

    Article  PubMed  CAS  Google Scholar 

  2. Ahmadi F, Asilian A, Ansarin H, Hallajy Z, Dolaty Y, Sodeify M, et al. editors. An introduction to skin diseases. Tehran: Tabib; 2000. p. 154–65

  3. LM Grisham L Wilson KG Bensch (1973) ArticleTitleAntimitotic action of griseofulvin does not involve disruption of microtubules Nature 244 294–6 Occurrence Handle4583106 Occurrence Handle10.1038/244294a0 Occurrence Handle1:CAS:528:DyaE3sXltFWqsbY%3D

    Article  PubMed  CAS  Google Scholar 

  4. L Wilson J Bryan (1973) ArticleTitleBiochemical and pharmacological properties of microtubules Adv Cell Mol Biol 3 21–7

    Google Scholar 

  5. A Roobol K Gull CI Pogson (1976) ArticleTitleInhibition by griseofulvin of microtubule assembly in vitro FEBS Lett 67 248–51 Occurrence Handle964356 Occurrence Handle10.1016/0014-5793(76)80539-X Occurrence Handle1:CAS:528:DyaE28XlslWmtLk%3D

    Article  PubMed  CAS  Google Scholar 

  6. RD Sloboda G Van Blaricom WA Creasey JL Rosenbaum SE Malawista (1982) ArticleTitleGriseofulvin: association with tubulin and inhibition of in vitro microtubule assembly Biochem Biophys Res Commun 105 882–8 Occurrence Handle7092906 Occurrence Handle10.1016/0006-291X(82)91052-X Occurrence Handle1:CAS:528:DyaL38XhslKms7c%3D

    Article  PubMed  CAS  Google Scholar 

  7. J Wehland W Herzog K Weber (1977) ArticleTitleInteraction of griseofulvin with microtubules, microtubule protein and tubulin J Mol Biol 111 329–42 Occurrence Handle864701 Occurrence Handle10.1016/S0022-2836(77)80055-7 Occurrence Handle1:CAS:528:DyaE2sXkslyhurw%3D

    Article  PubMed  CAS  Google Scholar 

  8. A Roobol K Gull CI Pogson (1977) ArticleTitleEvidence that griseofulvin binds to a microtubule associated protein FEBS Lett 75 149–53 Occurrence Handle852576 Occurrence Handle10.1016/0014-5793(77)80073-2 Occurrence Handle1:CAS:528:DyaE2sXktFKns7c%3D

    Article  PubMed  CAS  Google Scholar 

  9. DW Cleveland (1988) ArticleTitleAutoregulated instability of tubulin mRNAs: a novel eukaryotic regulatory mechanism Trends Biochem Sci 13 339–43 Occurrence Handle3072712 Occurrence Handle10.1016/0968-0004(88)90103-X Occurrence Handle1:CAS:528:DyaL1cXmt1Cktb8%3D

    Article  PubMed  CAS  Google Scholar 

  10. AR Chaudhuri RF Luduena (1996) ArticleTitleGriseofulvin: a novel interaction with bovine brain tubulin Biochem Pharmacol 51 903–9 Occurrence Handle8651940 Occurrence Handle10.1016/0006-2952(95)02406-9 Occurrence Handle1:CAS:528:DyaK28XitVCltr0%3D

    Article  PubMed  CAS  Google Scholar 

  11. EJ Anaissie MR McGinnis MA Pfaller (2003) Clinical mycology Churchill Livingstone Philadelphia PA, USA

    Google Scholar 

  12. C Lacroix M Baspeyras P de La Salmoniere M Benderdouche B Couprie I Accoceberry et al. (2002) ArticleTitleTinea pedis in European marathon runners J Eur Acad Dermatol Venereol 16 139–42 Occurrence Handle12046817 Occurrence Handle10.1046/j.1468-3083.2002.00400.x Occurrence Handle1:STN:280:DC%2BD38zgsFGrtA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  13. N Zaias G Rebell (1996) ArticleTitleChronic dermatophytosis syndrome due to Trichophyton rubrum Int J Dermatol 35 614–7 Occurrence Handle8876284 Occurrence Handle10.1111/j.1365-4362.1996.tb03682.x Occurrence Handle1:STN:280:ByiD3s%2FjsVc%3D

    Article  PubMed  CAS  Google Scholar 

  14. M Chadeganipour S Nilipour A Havaei (2004) ArticleTitleIn vitro evaluation of griseofulvin against clinical isolates of dermatophytes from Isfahan Mycoses 47 503–7 Occurrence Handle15601457 Occurrence Handle10.1111/j.1439-0507.2004.01050.x Occurrence Handle1:CAS:528:DC%2BD2MXhtVCms78%3D

    Article  PubMed  CAS  Google Scholar 

  15. AL Fachin EP Contel NM Martinez-Rossi (2001) ArticleTitleEffect of sub-MICs of antimycotics on expression of intracellular esterase of Trichophyton rubrum Med Mycol 39 129–33 Occurrence Handle11270400 Occurrence Handle10.1080/714030995 Occurrence Handle1:CAS:528:DC%2BD3MXisVGltLg%3D

    Article  PubMed  CAS  Google Scholar 

  16. AL Fachin MS Ferreira-Nozawa WJ Maccheroni NM Martinez-Rossi (2006) ArticleTitleRole of the ABC transporter TruMDR2 in terbinafine, 4-nitroquinoline N-oxide and ethidium bromide susceptibility in Trichophyton rubrum J Med Microbiol 55 1093–9 Occurrence Handle16849730 Occurrence Handle10.1099/jmm.0.46522-0 Occurrence Handle1:CAS:528:DC%2BD28Xptlehu7k%3D

    Article  PubMed  CAS  Google Scholar 

  17. S Rezaie J Ban M Mildner C Poitschek C Brna E Tschachler (2000) ArticleTitleCharacterization of a cDNA clone, encoding a 70 kDa heat shock protein from the dermatophyte pathogen Trichophyton rubrum Gene 241 27–33 Occurrence Handle10607895 Occurrence Handle10.1016/S0378-1119(99)00475-8 Occurrence Handle1:CAS:528:DyaK1MXotVGlu7c%3D

    Article  PubMed  CAS  Google Scholar 

  18. Maniatis T, Fritsch EF, Smabrook J, editors. Molecular cloning (a laboratory manual). Cold Spring Harbor: Cold Spring Harbor Laboratory; 1989

  19. B Bjellqvist B Basse E Olsen JE Celis (1994) ArticleTitleReference points for comparisons of two-dimensional maps of proteins from different human cell types defined in a pH scale where isoelectric points correlate with polypeptide compositions Electrophoresis 15 529–39 Occurrence Handle8055880 Occurrence Handle10.1002/elps.1150150171 Occurrence Handle1:CAS:528:DyaK2cXjtFyltrk%3D

    Article  PubMed  CAS  Google Scholar 

  20. B Bjellqvist GJ Hughes C Pasquali N Paquet F Ravier JC Sanchez et al. (1993) ArticleTitleThe focusing positions of polypeptides in immobilized pH gradients can be predicted from their amino acid sequences Electrophoresis 14 1023–31 Occurrence Handle8125050 Occurrence Handle10.1002/elps.11501401163 Occurrence Handle1:CAS:528:DyaK2cXis1ynsQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  21. E Gasteiger C Hoogland A Gattiker S Duvaud MR Wilkins RD Appel et al. (2005) Protein identification and analysis tools on the ExPASy server JM Walker (Eds) The proteomics protocols handbook Humana Totawa, NJ, USA 571–607

    Google Scholar 

  22. M Madera C Vogel SK Kummerfeld C Chothia J Gough (2004) ArticleTitleThe superfamily database in 2004: additions and improvements Nucleic Acids Res 32 D235–9 Occurrence Handle14681402 Occurrence Handle10.1093/nar/gkh117 Occurrence Handle1:CAS:528:DC%2BD3sXhtVSru7zJ

    Article  PubMed  CAS  Google Scholar 

  23. IB Rogozin AV Kochetov FA Kondrashov EV Koonin L Milanesi (2001) ArticleTitlePresence of ATG triplets in 5′ untranslated regions of eukaryotic cDNAs correlates with a “weak” context of the start codon Bioinformatics 17 890–900 Occurrence Handle11673233 Occurrence Handle10.1093/bioinformatics/17.10.890 Occurrence Handle1:CAS:528:DC%2BD3MXot1Ggtb0%3D

    Article  PubMed  CAS  Google Scholar 

  24. HA Norris BE Elewski MA Ghannoum (2000) ArticleTitleOptimal growth conditions for the determination of the antifungal susceptibility of three species of dermatophytes with the use of a microdilution method J Am Acad Dermatol 40 S9–S13 Occurrence Handle10.1016/S0190-9622(99)70392-0

    Article  Google Scholar 

  25. MA Ghannoum V Chaturvedi A Espinel-Ingroff MA Pfaller MG Rinaldi W Lee-Yang et al. (2004) ArticleTitleIntra- and inter-laboratory study of a method for testing the antifungal susceptibilities of dermatophytes J Clin Microbiol 42 2977–9 Occurrence Handle15243047 Occurrence Handle10.1128/JCM.42.7.2977-2979.2004 Occurrence Handle1:CAS:528:DC%2BD2cXntFGksbg%3D

    Article  PubMed  CAS  Google Scholar 

  26. MW Pfaffl (2001) ArticleTitleA new mathematical model for relative quantification in real-time RT-PCR Nucleic Acids Res 29 e45 Occurrence Handle11328886 Occurrence Handle10.1093/nar/29.9.e45 Occurrence Handle1:STN:280:DC%2BD38nis12jtw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  27. HC Joshi DW Cleveland (1990) ArticleTitleDiversity among tubulin subunits: toward what functional end? Cell Motil Cytoskeleton 16 159–63 Occurrence Handle2194680 Occurrence Handle10.1002/cm.970160302 Occurrence Handle1:CAS:528:DyaK3cXls1Onsbo%3D

    Article  PubMed  CAS  Google Scholar 

  28. MA Kassem S Esmat ER Bendas MH El-Komy (2006) ArticleTitleEfficacy of topical griseofulvin in treatment of tinea corporis Mycoses 49 232–5 Occurrence Handle16681816 Occurrence Handle10.1111/j.1439-0507.2006.01221.x Occurrence Handle1:CAS:528:DC%2BD28Xls1Crtro%3D

    Article  PubMed  CAS  Google Scholar 

  29. K Gull APJ Trinci (1973) ArticleTitleGriseofulvin inhibits fungal mitosis Nature 244 292–4 Occurrence Handle4583105 Occurrence Handle10.1038/244292a0 Occurrence Handle1:CAS:528:DyaE3sXltlehtL8%3D

    Article  PubMed  CAS  Google Scholar 

  30. K Sen GN Godson (1990) ArticleTitleIsolation of alpha- and beta-tubulin genes of Plasmodium falciparum using a single oligonucleotide probe Mol Biochem Parasitol 39 173–82 Occurrence Handle2181306 Occurrence Handle10.1016/0166-6851(90)90056-R Occurrence Handle1:CAS:528:DyaK3cXkslaitbo%3D

    Article  PubMed  CAS  Google Scholar 

  31. KF Sullivan DW Cleveland (1984) ArticleTitleSequence of a highly divergent beta tubulin gene reveals regional heterogeneity in the beta tubulin polypeptide J Cell Biol 99 1754–60 Occurrence Handle6490718 Occurrence Handle10.1083/jcb.99.5.1754 Occurrence Handle1:CAS:528:DyaL2MXlslSgtA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  32. TD Edlind MS Bartlett GA Weinberg GN Prah JW Smith (1992) ArticleTitleThe beta-tubulin gene from rat and human isolates of Pneumocystis carinii Mol Microbiol 6 3365–73 Occurrence Handle1484490 Occurrence Handle10.1111/j.1365-2958.1992.tb02204.x Occurrence Handle1:CAS:528:DyaK3sXkvVOkt74%3D

    Article  PubMed  CAS  Google Scholar 

  33. GS May ML Tsang H Smith S Fidel NR Morris (1987) ArticleTitle Aspergillus nidulans beta-tubulin genes are unusually divergent Gene 55 231–43 Occurrence Handle2959591 Occurrence Handle10.1016/0378-1119(87)90283-6 Occurrence Handle1:CAS:528:DyaL1cXltVeisA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  34. HA Smith HS Allaudeen MH Whitman Y Koltin JA Gorman (1988) ArticleTitleIsolation and characterization of a beta-tubulin gene from Candida albicans Gene 63 53–63 Occurrence Handle3290053 Occurrence Handle10.1016/0378-1119(88)90545-8 Occurrence Handle1:CAS:528:DyaL1cXlt1ens7k%3D

    Article  PubMed  CAS  Google Scholar 

  35. TS Wu CD Skory JS Horng JE Linz (1996) ArticleTitleCloning and functional analysis of a beta-tubulin gene from a benomyl resistant mutant of Aspergillus parasiticus Gene 182 7–12 Occurrence Handle8982061 Occurrence Handle10.1016/S0378-1119(96)00382-4 Occurrence Handle1:CAS:528:DyaK28XntlOhs7g%3D

    Article  PubMed  CAS  Google Scholar 

  36. J Hesse M Thierauf H Ponstingl (1987) ArticleTitleTubulin sequence region beta 155–174 is involved in binding exchangeable guanosine triphosphate J Biol Chem 262 15 472–5 Occurrence Handle1:CAS:528:DyaL2sXlvFensr4%3D

    CAS  Google Scholar 

  37. TJ Yen PS Machlin DW Cleveland (1988) ArticleTitleAutoregulated instability of beta-tubulin mRNAs by recognition of the nascent amino terminus of beta-tubulin Nature 334 580–5 Occurrence Handle3405308 Occurrence Handle10.1038/334580a0 Occurrence Handle1:CAS:528:DyaL1cXlsVCkt7k%3D

    Article  PubMed  CAS  Google Scholar 

  38. HP Erickson (1995) ArticleTitleFtsZ, a prokaryotic homolog of tubulin? Cell 80 367–70 Occurrence Handle7859278 Occurrence Handle10.1016/0092-8674(95)90486-7 Occurrence Handle1:CAS:528:DyaK2MXjslWkt70%3D

    Article  PubMed  CAS  Google Scholar 

  39. J Lowe LA Amos (1998) ArticleTitleCrystal structure of the bacterial cell-division protein FtsZ Nature 391 203–6 Occurrence Handle9428770 Occurrence Handle10.1038/34472 Occurrence Handle1:CAS:528:DyaK1cXmt1KisA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  40. E Nogales SG Wolf KH Downing (1998) ArticleTitleStructure of the alpha beta tubulin dimer by electron crystallography Nature 391 199–203 Occurrence Handle9428769 Occurrence Handle10.1038/34465 Occurrence Handle1:CAS:528:DyaK1cXmt1Kisw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  41. E Nogales KH Downing LA Amos J Lowe (1998) ArticleTitleTubulin and FtsZ form a distinct family of GTPases Nat Struct Biol 5 451–8 Occurrence Handle9628483 Occurrence Handle10.1038/nsb0698-451 Occurrence Handle1:CAS:528:DyaK1cXjslCktLY%3D

    Article  PubMed  CAS  Google Scholar 

  42. PJ Schatz F Solomon D Botstein (1986) ArticleTitleGenetically essential and nonessential α-tubulin genes specify functionally interchangeable proteins Mol Cell Biol 63 722–37

    Google Scholar 

  43. D Burke P Gasdaska L Hartwell (1989) ArticleTitleDominant effects of tubulin overexpression in Saccharomyces cerevisiae Mol Cell Biol 9 1049–59 Occurrence Handle2657385 Occurrence Handle1:CAS:528:DyaL1MXhslSjtbg%3D

    PubMed  CAS  Google Scholar 

  44. J Javerzat G Cranston RC Allshire (1996) ArticleTitleFission yeast genes which disrupt mitotic chromosome segregation when overexpressed Nucleic Acids Res 24 4676–83 Occurrence Handle8972853 Occurrence Handle10.1093/nar/24.23.4676 Occurrence Handle1:CAS:528:DyaK2sXmsV2n

    Article  PubMed  CAS  Google Scholar 

  45. L Vega J Fleming F Solomon (1998) ArticleTitleAn α-tubulin mutant destabilizes the heterodimer: phenotypic consequences and interactions with tubulin-binding proteins Mol Biol Cell 9 2349–60 Occurrence Handle9725898 Occurrence Handle1:CAS:528:DyaK1cXmtFSrtLg%3D

    PubMed  CAS  Google Scholar 

  46. B Weinstein F Solomon (1990) ArticleTitlePhenotypic consequences of tubulin overproduction in Saccharomyces cerevisiae: differences between alpha-tubulin and beta-tubulin Mol Cell Biol 10 5295–304 Occurrence Handle2204812 Occurrence Handle1:CAS:528:DyaK3cXlvVOqt7k%3D

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Mycology and Parasitology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Kamiar Zomorodian

  2. Department of Immunodermatology, Vienna Medical University, Vienna, Austria

    Umed Uthman

  3. Department of Medical Mycology and Parasitology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Bita Tarazooie & Sassan Rezaie

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  1. Kamiar Zomorodian
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  2. Umed Uthman
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  3. Bita Tarazooie
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  4. Sassan Rezaie
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Correspondence to Kamiar Zomorodian.

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Zomorodian, K., Uthman, U., Tarazooie, B. et al. The effect of griseofulvin on the gene regulation of β-tubulin in the dermatophyte pathogen Trichophyton rubrum . J Infect Chemother 13, 373–379 (2007). https://doi.org/10.1007/s10156-007-0552-5

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