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Allicin-induced global gene expression profile of Saccharomyces cerevisiae

  • Genomics, Transcriptomics, Proteomics
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

To understand the response mechanisms of fungus cells upon exposure to the natural fungicide allicin, we performed commercial oligonucleotide microarrays to determine the overall transcriptional response of allicin-treated Saccharomyces cerevisiae strain L1190. Compared with the transcriptional profiles of untreated cultures, 147 genes were significantly upregulated, and 145 genes were significantly downregulated in the allicin-treated cells. We interpreted the microarray data with the hierarchical clustering tool, T-profiler. Major transcriptional responses were induced by allicin and included the following: first, Rpn4p-mediated responses involved in proteasome gene expression; second, the Rsc1p-mediated response involved in iron ion transporter activity; third, the Gcn4p-mediated response, also known as general amino acid control; finally, the Yap1p-, Msn2/4p-, Crz1p-, and Cin5p-mediated multiple stress response. Interestingly, allicin treatment, similar to mycotoxin patulin and artificial fungicide thiuram treatment, was found to induce genes involved in sulfur amino acid metabolism and the defense system for oxidative stress, especially DNA repair, which suggests a potential mutagenicity for allicin. Quantitative real-time reverse transcription-polymerase chain reaction was performed for selected genes to verify the microarray results. To our knowledge, this is the first report of the global transcriptional profiling of allicin-treated S. cerevisiae by microarray.

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References

  • Adetumbi M, Javor GT, Lau BH (1986) Allium sativum (garlic) inhibits lipid synthesis by Candida albicans. Antimicrob Agents Chemother 30:499–501

    CAS  Google Scholar 

  • Agarwal AK, Rogers PD, Baerson SR, Jacob MR, Barker KS, Cleary JD, Walker LA, Nagle DG, Clark AM (2003) Genome-wide expression profiling of the response to polyene, pyrimidine, azole, and echinocandin antifungal agents in Saccharomyces cerevisiae. J Biol Chem 278:34998–35015

    Article  CAS  Google Scholar 

  • An M, Shen H, Cao Y, Zhang J, Cai Y, Wang R, Jiang Y (2009) Allicin enhances the oxidative damage effect of amphotericin B against Candida albicans. Int J Antimicrob Agents 33:258–263

    Article  CAS  Google Scholar 

  • Ankri S, Mirelman D (1999) Antimicrobial properties of allicin from garlic. Microbes Infect 1:125–129

    Article  CAS  Google Scholar 

  • Arditti FD, Rabinkov A, Miron T, Reisner Y, Berrebi A, Wilchek M, Mirelman D (2005) Apoptotic killing of B-chronic lymphocytic leukemia tumor cells by allicin generated in situ using a rituximab-alliinase conjugate. Mol Cancer Ther 4:325–331

    CAS  Google Scholar 

  • Arroyo J, Bermejo C, García R, Rodríguez-Peña JM (2009) Genomics in the detection of damage in microbial systems: cell wall stress in yeast. Clin Microbiol Suppl 1:44–46

    Google Scholar 

  • Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G (2000) Gene ontology: tool for the unification of biology. The gene ontology consortium. Nat Genet 25:25–29

    Article  CAS  Google Scholar 

  • Bammert GF, Fostel JM (2000) Genome-wide expression patterns in Saccharomyces cerevisiae: comparison of drug treatments and genetic alterations affecting biosynthesis of ergosterol. Antimicrob Agents Chemother 44:1255–1265

    Article  CAS  Google Scholar 

  • Banting GS, Glerum DM (2006) Mutational analysis of the Saccharomyces cerevisiae cytochrome c oxidase assembly protein Cox11p. Eukaryot Cell 5:568–578

    Article  CAS  Google Scholar 

  • Cavalieri D, Townsend JP, Hartl DL (2000) Manifold anomalies in gene expression in a vineyard isolate of Saccharomyces cerevisiae revealed by DNA microarray analysis. Proc Natl Acad Sci U S A 97:12369–12374

    Article  CAS  Google Scholar 

  • Collart MA, Oliviero S (1995) In short protocols in molecular biology. In: Ausubel F, Brent R, Kingston RT et al (eds) Preparation of yeast RNA, 3rd edn. Wiley, New York, pp 13-46–13-47

    Google Scholar 

  • Dickinson JR, Salgado LE, Hewlins MJ (2003) The catabolism of amino acids to long chain and complex alcohols in Saccharomyces cerevisiae. J Biol Chem 278:8028–8034

    Article  CAS  Google Scholar 

  • Fragiadakis GS, Tzamarias D, Alexandraki D (2004) Nhp6 facilitates Aft1 binding and Ssn6 recruitment, both essential for FRE2 transcriptional activation. EMBO J 23:333–342

    Article  CAS  Google Scholar 

  • Franekić J, Bratulić N, Pavlica M, Papes D (1994) Genotoxicity of dithiocarbamates and their metabolites. Mutat Res 325:65–74

    Article  Google Scholar 

  • Furuchi T, Ishikawa H, Miura N, Ishizuka M, Kajiya K, Kuge S, Naganuma A (2001) Two nuclear proteins, Cin5 and Ydr259c, confer resistance to cisplatin in Saccharomyces cerevisiae. Mol Pharmacol 59:470–474

    CAS  Google Scholar 

  • García R, Bermejo C, Grau C, Pérez R, Rodríguez-Peña JM, Francois J, Nombela C, Arroyo J (2004) The global transcriptional response to transient cell wall damage in Saccharomyces cerevisiae and its regulation by the cell integrity signaling pathway. J Biol Chem 279:15183–15195

    Article  Google Scholar 

  • Gasch AP (2003) The environmental stress response: a common yeast response to diverse environmental stresses. Curr Top Genet 1:11–70

    Article  CAS  Google Scholar 

  • Gasch AP, Spellman PT, Kao CM, Carmel-Harel O, Eisen MB, Storz G, Botstein D, Brown PO (2000) Genomic expression programs in the response of yeast cells to environmental changes. Mol Biol Cell 11:4241–4257

    CAS  Google Scholar 

  • Ghannoum MA (1988) Studies on the anticandidal mode of action of Allium sativum (garlic). J Gen Microbiol 134(11):2917–2924

    CAS  Google Scholar 

  • Groll AH, Piscitelli SC, Walsh TJ (1998) Clinical pharmacology of systemic antifungal agents: a comprehensive review of agents in clinical use, current investigational compounds, and putative targets for antifungal drug development. Adv Pharmacol 44:343–500

    Article  CAS  Google Scholar 

  • Guo Y, Guo H, Zhang L, Xie H, Zhao X, Wang F, Li Z, Wang Y, Ma S, Tao J, Wang W, Zhou Y, Yang W, Cheng J (2005) Genomic analysis of anti-hepatitis B virus (HBV) activity by small interfering RNA and lamivudine in stable HBV-producing cells. J Virol 79:14392–14403

    Article  CAS  Google Scholar 

  • Guo N, Yu L, Meng R, Fan J, Wang D, Sun G, Deng X (2008) Global gene expression profile of Saccharomyces cerevisiae induced by dictamnine. Yeast 25:631–641

    Article  CAS  Google Scholar 

  • Han J, Lawson L, Han G, Han P (1995) A spectrophotometric method for quantitative determination of allicin and total garlic thiosulfinates. Anal Biochem 225:157–160

    Article  CAS  Google Scholar 

  • Hohmann S, Meacock PA (1998) Thiamin metabolism and thiamin diphosphate-dependent enzymes in the yeast Saccharomyces cerevisiae: genetic regulation. Biochim Biophys Acta 1385:201–219

    CAS  Google Scholar 

  • Iwahashi Y, Hosoda H, Park JH, Lee JH, Suzuki Y, Kitagawa E, Murata SM, Jwa NS, Gu MB, Iwahashi H (2006) Mechanisms of patulin toxicity under conditions that inhibit yeast growth. J Agric Food Chem 54:1936–1942

    Article  CAS  Google Scholar 

  • Iwahashi H, Kitagawa E, Suzuki Y, Ueda Y, Ishizawa YH, Nobumasa H, Kuboki Y, Hosoda H, Iwahashi Y (2007) Evaluation of toxicity of the mycotoxin citrinin using yeast ORF DNA microarray and Oligo DNA microarray. BMC Genomics 8:95

    Article  Google Scholar 

  • Kitagawa E, Takahashi J, Momose Y, Iwahashi H (2002) Effects of the pesticide thiuram: genome-wide screening of indicator genes by yeast DNA microarray. Environ Sci Technol 36:3908–3915

    Article  CAS  Google Scholar 

  • Kitagawa E, Momose Y, Iwahashi H (2003) Correlation of the structures of agricultural fungicides to gene expression in Saccharomyces cerevisiae upon exposure to toxic doses. Environ Sci Technol 37:2788–2793

    Article  CAS  Google Scholar 

  • Lemar KM, Turner MP, Lloyd D (2002) Garlic (Allium sativum) as an anti-Candida agent: a comparison of the efficacy of fresh garlic and freeze-dried extracts. J Appl Microbiol 93:398–405

    Article  CAS  Google Scholar 

  • Lu L, Roberts G, Simon K, Yu J, Hudson AP (2003) Rsf1p, a protein required for respiratory growth of Saccharomyces cerevisiae. Curr Genet 43:263–272

    Article  CAS  Google Scholar 

  • Mao X, Cai T, Olyarchuk JG, Wei L (2005) Automated genome annotation and pathway identification using the KEGG Orthology (KO) as a controlled vocabulary. Bioinformatics 21:3787–3793

    Article  CAS  Google Scholar 

  • Meyer V, Damveld RA, Arentshorst M, Stahl U, van den Hondel CA, Ram AF (2007) Survival in the presence of antifungals: genome-wide expression profiling of Aspergillus niger in response to sublethal concentrations of caspofungin and fenpropimorph. J Biol Chem 282:32935–32948

    Article  CAS  Google Scholar 

  • Miron T, Mironchik M, Mirelman D, Wilchek M, Rabinkov A (2003) Inhibition of tumor growth by a novel approach: in situ allicin generation using targeted alliinase delivery. Mol Cancer Ther 2:1295–1301

    CAS  Google Scholar 

  • Murata Y, Watanabe T, Sato M, Momose Y, Nakahara T, Shu-ichi O, Iwahashi H (2003) Dimethyl sulfoxide exposure facilitates phospholipid biosynthesis and cellular membrane proliferation in yeast cells. J Biol Chem 278:33185–33193

    Article  CAS  Google Scholar 

  • Mutch DM, Berger A, Mansourian R, Rytz A, Roberts MA (2002) The limit fold change model: a practical approach for selecting differentially expressed genes from microarray data. BMC Bioinform 21:3–17

    Google Scholar 

  • Nevitt T, Pereira J, Azevedo D, Guerreiro P, Rodrigues-Pousada C (2004) Expression of YAP4 in Saccharomyces cerevisiae under osmotic stress. Biochem J 379:367–374

    Article  CAS  Google Scholar 

  • Nosaka K (2006) Recent progress in understanding thiamin biosynthesis and its genetic regulation in Saccharomyces cerevisiae. Appl Microbiol Biotechnol 72:30–40

    Article  CAS  Google Scholar 

  • Nosaka K, Onozuka M, Konno H, Akaji K (2008) Thiamin-dependent transactivation activity of PDC2 in Saccharomyces cerevisiae. FEBS Lett 582:3991–3996

    Article  CAS  Google Scholar 

  • Owsianik G, Balzi IL, Ghislain M (2002) Control of 26S proteasome expression by transcription factors regulating multidrug resistance in Saccharomyces cerevisiae. Mol Microbiol 43:1295–1308

    Article  CAS  Google Scholar 

  • Parveen M, Hasan MK, Takahashi J, Murata Y, Kitagawa E, Kodama O, Iwahashi H (2004) Response of Saccharomyces cerevisiae to a monoterpene: evaluation of antifungal potential by DNA microarray analysis. J Antimicrob Chemother 54:46–55

    Article  CAS  Google Scholar 

  • Pyun MS, Shin S (2006) Antifungal effects of the volatile oils from Allium plants against Trichophyton species and synergism of the oils with ketocona. Phytomedicine 13:394–400

    Article  CAS  Google Scholar 

  • Rabinkov A, Miron T, Mirelman D, Wilchek M, Glozman S, Yavin E, Weiner L (2000) S-allylmercaptoglutathione: the reaction product of allicin with glutathione possesses SH-modifying and antioxidant properties. Biochim Biophys Acta 1499:144–153

    Article  CAS  Google Scholar 

  • Regenberg B, Grotkjaer T, Winther O, Fausbøll A, Akesson M, Bro C, Hansen LK, Brunak S, Nielsen J (2006) Growth-rate regulated genes have profound impact on interpretation of transcriptome profiling in Saccharomyces cerevisiae. Genome Biol 7:R107

    Article  Google Scholar 

  • Samanta MP, Liang S (2003) Predicting protein functions from redundancies in large-scale protein interaction networks. Proc Natl Acad Sci U S A 100:12579–12583

    Article  CAS  Google Scholar 

  • Schuurmans JM, Boorsma A, Lascaris R, Hellingwerf KJ, Teixeira de Mattos MJ (2008) Physiological and transcriptional characterization of Saccharomyces cerevisiae strains with modifed expression of catabolic regulators. FEMS Yeast Res 8:26–34

    Article  CAS  Google Scholar 

  • Sha G, Wu D, Zhang L, Chen X, Lei M, Sun H, Lin S, Lang J (2007) Differentially expressed genes in human endometrial endothelial cells derived from eutopic endometrium of patients with endometriosis compared with those from patients without endometriosis. Hum Reprod 22:3159–3169

    Article  CAS  Google Scholar 

  • Shadkchan Y, Shemesh E, Mirelman D, Miron T, Rabinkov A, Wilchek M, Osherov N (2004) Efficacy of allicin, the reactive molecule of garlic, in inhibiting Aspergillus spp. in vitro, and in a murine model of disseminated aspergillosis. J Antimicrob Chemother 53:832–836

    Article  CAS  Google Scholar 

  • Shakoury-Elizeh M, Tiedeman J, Rashford J, Ferea T, Demeter J, Garcia E, Rolfes R, Brown PO, Botstein D, Philpott CC (2004) Transcriptional remodeling in response to iron deprivation in Saccharomyces cerevisiae. Mol Biol Cell 15:1233–1243

    Article  CAS  Google Scholar 

  • Smith MG, Des Etages SG, Snyder M (2004) Microbial synergy via an ethanol-triggered pathway. Mol Cell Biol 24:3874–3884

    Article  CAS  Google Scholar 

  • Sun H, Yuan Y, Wu Y, Liu H, Liu JS, Xie H (2010) Tmod: toolbox of motif discovery. Bioinformatics 26:405–407

    Article  CAS  Google Scholar 

  • Teixeira MC, Dias PJ, Simões T, Sá-Correia I (2008) Yeast adaptation to mancozeb involves the up-regulation of FLR1 under the coordinate control of Yap1, Rpn4, Pdr3, and Yrr1. Biochem Biophys Res Commun 367:249–255

    Article  CAS  Google Scholar 

  • Wightman R, Meacock PA (2003) The THI5 gene family of Saccharomyces cerevisiae: distribution of homologues among the hemiascomycetes and functional redundancy in the aerobic biosynthesis of thiamin from pyridoxine. Microbiology 149:1447–1460

    Article  CAS  Google Scholar 

  • Wills ED (1956) Enzyme inhibition by allicin, the active principle of garlic. Biochem J 63:514–520

    CAS  Google Scholar 

  • Xiao W, Samson L (1992) The Saccharomyces cerevisiae MGT1 DNA repair methyltransferase gene: its promoter and entire coding sequence, regulation and in vivo biological functions. Nucleic Acids Res 20:3599–3606

    Article  CAS  Google Scholar 

  • Yamada Y, Azuma K (1997) Evaluation of the in vitro antifungal activity of allicin. Antimicrob Agents Chemother 11:743–749

    Google Scholar 

  • Yang R, Wek SA, Wek RC (2000) Glucose limitation induces GCN4 translation by activation of Gcn2 protein kinase. Mol Cell Biol 20:2706–2717

    Article  CAS  Google Scholar 

  • Yang YH, Dudoit S, Luu P, Lin DM, Peng V, Ngai J, Speed TP (2002) Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation. Nucleic Acids Res 30:e15

    Article  Google Scholar 

  • Yoshida S, Kasuga S, Hayashi N, Ushiroguchi T, Matsuura H, Nakagawa S (1987) Antifungal activity of ajoene derived from garlic. Appl Environ Microbiol 53:615–617

    CAS  Google Scholar 

  • Yu L, Zhang W, Wang L, Yang J, Liu T, Peng J, Leng W, Chen L, Li R, Jin Q (2007) Transcriptional profiles of the response to ketoconazole and amphotericin B in Trichophyton rubrum. Antimicrob Agents Chemother 51:144–153

    Article  CAS  Google Scholar 

  • Zakrzewska A, Boorsma A, Brul S, Hellingwerf KJ, Klis FM (2005) Transcriptional response of Saccharomyces cerevisiae to the plasma membrane-perturbing compound chitosan. Eukaryot Cell 4:703–715

    Article  CAS  Google Scholar 

  • Zakrzewska A, Boorsma A, Delneri D, Brul S, Oliver SG, Klis FM (2007) Cellular processes and pathways that protect Saccharomyces cerevisiae cells against the plasma membrane-perturbing compound chitosan. Eukaryot Cell 6:600–608

    Article  CAS  Google Scholar 

  • Zhang L, Zhang Y, Zhou Y, An S, Zhou Y, Cheng J (2002) Response of gene expression in Saccharomyces cerevisiae to amphotericin B and nystatin measured by microarrays. J Antimicrob Chemother 49:905–915

    Article  CAS  Google Scholar 

  • Zhang W, Needham DL, Coffin M, Rooker A, Hurban P, Tanzer MM, Shuster JR (2003) Microarray analyses of the metabolic responses of Saccharomyces cerevisiae to organic solvent dimethyl sulfoxide. J Ind Microbiol Biotechnol 30:57–69

    CAS  Google Scholar 

  • Zhou SM, Jiang LP, Geng CY, Cao J, Zhong LF (2009) Patulin-induced genotoxicity and modulation of glutathione in HepG2 cells. Toxicon 53:584–586

    Article  CAS  Google Scholar 

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Acknowledgements

We are grateful to Dr. Liang Zhang (CapitalBio) for oligonucleotide microarray work and for helpful discussions. This work was supported by the National Basic Research Program (973 program; 2006CB504402) and Important National Science and Technology Specific Projects (2008ZX10301).

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Authors and Affiliations

  1. Laboratory of Nutrition and Functional Food, Jilin University, Changchun, 5333 Xi’an Road, 130062, People’s Republic of China

    Na Guo

  2. Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, 5333 Xi’an Road, Changchun, 130062, People’s Republic of China

    Lu Yu, Jing Jin, Yumei Cui & Xuming Deng

  3. Department of Hand Surgery, First Hospital of Jilin University, Changchun, 130021, People’s Republic of China

    Bin Liu

  4. Jilin Entry-Exit Inspection and Quarantine Bureau, Changchun, 130062, People’s Republic of China

    Rizeng Meng

  5. Key Lab for New Drug Research of TCM, Research Institute of Tsinghua University in Shenzhen, Shenzhen, 518057, People’s Republic of China

    Xudong Tang

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  1. Lu Yu
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  3. Rizeng Meng
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Yu, L., Guo, N., Meng, R. et al. Allicin-induced global gene expression profile of Saccharomyces cerevisiae . Appl Microbiol Biotechnol 88, 219–229 (2010). https://doi.org/10.1007/s00253-010-2709-x

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