Article Search
닫기

Microbiology and Biotechnology Letters

보문(Article)

View PDF

Molecular and Cellular Microbiology (MCM)  |  Microbial Genetics, Physiology and Metabolism

Microbiol. Biotechnol. Lett.

Received: February 16, 2022; Revised: June 3, 2022; Accepted: June 2, 2022

Zerumbone 처리 헬리코박터 파이로리균의 전사체 분석 비교

Comparative Transcriptome Analysis of Zerumbone-Treated Helicobacter pylori

Hyun Jun Woo1†, Ji Yeong Yang2†, and Sa-Hyun Kim1*

1Department of Clinical Laboratory Science, Semyung University, Jaecheon 27136, Republic of Korea 2Division of Crop Foundation, National Institute of Crop Science (NICS), Rural Development Administration (RDA), Wanju 55365, Republic of Korea

Correspondence to :
Sa-Hyun Kim,       science4us@semyung.ac.kr

Helicobacter pylori (H. pylori) establishes infection in the human gastric mucosa for a long time and causes severe gastric diseases such as peptic ulcer and gastric cancer. When H. pylori is exposed to the antibacterial agents or inhibitors, the expression of pathogenic associated genes could be altered. In this study, we analyzed the transcriptional changes of H. pylori genes induced by zerumbone treatment. RNA expression changes were analyzed using next-generation sequencing (NGS), and then reverse transcription-polymerase chain reaction (RT-PCR) was performed to verify the results. As a result of NGS analysis, a total of 23 out of 1,632 genes were differentially expressed by zerumbone treatment. RT-PCR confirmed that zerumbone treatment regulated the expression level of 14 genes. Among the genes associated with DNA replication, transcription, virulence factors and T4SS components, 10 genes (dnaE, dnaQ, rpoA, rpoD, secA, flgE, flhA, virB5, virB8 and virB9) were significantly down-regulated and 4 genes (flaA, flaB, virB4 and virD4) were up-regulated. The results of our current study imply that zerumbone might be a potential therapeutic agent for H. pylori infection by regulating factors related to various H. pylori pathogenicity.

Keywords: Helicobacter pylori, zerumbone, next-generation sequencing, RNA-sequencing

Graphical Abstract


  1. de Martel C, Ferlay J, Franceschi S, Vignat J, Bray F, Forman D, et al. 2012. Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol. 13: 607615.
  2. Marshall BJ, Warren JR. 1984. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1: 1311-1315.
  3. Warren JR, Marshall B. 1983. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1: 1273-1275.
  4. Amieva M, Peek RM, Jr. 2016. Pathobiology of Helicobacter pylori-induced gastric cancer. Gastroenterology 150: 64-78.
    Pubmed KoreaMed
  5. Salama NR, Hartung ML, Muller A. 2013. Life in the human stomach: persistence strategies of the bacterial pathogen Helicobacter pylori. Nat. Rev. Microbiol. 11: 385-399.
    Pubmed KoreaMed
  6. Wang F, Meng W, Wang B, Qiao L. 2014. Helicobacter pyloriinduced gastric inflammation and gastric cancer. Cancer Lett. 345: 196-202.
    Pubmed
  7. 1994. Schistosomes, liver flukes and Helicobacter pylori. IARC working group on the evaluation of carcinogenic risks to humans. lyon, 7-14 June 1994. IARC Monogr. Eval. Carcinog. Risks Hum. 61: 1-241.
  8. Vilaichone RK, Mahachai V, Shiota S, Uchida T, Ratanachu-ek T, Tshering L, et al. 2013. Extremely high prevalence of Helicobacter pylori infection in bhutan. World J. Gastroenterol. 19: 28062810.
    Pubmed KoreaMed
  9. Kalantari K, Moniri M, Boroumand Moghaddam A, Abdul Rahim R, Bin Ariff A, Izadiyan Z, et al. 2017. A review of the biomedical applications of zerumbone and the techniques for its extraction from ginger rhizomes. Molecules 22: 1645.
    Pubmed KoreaMed
  10. Ohnishi K, Irie K, Murakami A. 2009. In vitro covalent binding proteins of zerumbone, a chemopreventive food factor. Biosci. Biotechnol. Biochem. 73: 1905-1907.
    Pubmed
  11. Girisa S, Shabnam B, Monisha J, Fan L, Halim CE, Arfuso F, et al. 2019. Potential of zerumbone as an anti-cancer agent. Molecules 24: 734.
    Pubmed KoreaMed
  12. Rosa A, Caprioglio D, Isola R, Nieddu M, Appendino G, Falchi AM. 2019. Dietary zerumbone from shampoo ginger: new insights into its antioxidant and anticancer activity. Food Funct. 10: 1629-1642.
    Pubmed
  13. Sulaiman MR, Perimal EK, Akhtar MN, Mohamad AS, Khalid MH, Tasrip NA, et al. 2010. Anti-inflammatory effect of zerumbone on acute and chronic inflammation models in mice. Fitoterapia 81: 855-858.
    Pubmed
  14. Vishwanatha H, Babu PN, Gowrishankar B, Shridhar S. 2012. Antimicrobial activity of zerumbone from zingiber zurumbet against Staphylococcus epidermidis and Aspergillus spp. Int. J. Appl. Biol. Pharm. 3: 40-43.
  15. Sidahmed HMA, Hashim NM, Abdulla MA, Ali HM, Mohan S, Abdelwahab SI, et al. 2015. Antisecretory, gastroprotective, antioxidant and anti-Helicobcter pylori activity of zerumbone from Zingiber zerumbet (L.) Smith. PLoS One 10: e0121060.
    Pubmed KoreaMed
  16. Kim S-H. 2018. Comparative proteome analysis of zerumbonetreated Helicobacter pylori. Korean J. Clin. Lab. Sci. 50: 275-283.
  17. Woo HJ, Yang JY, Lee P, Kim JB, Kim SH. 2021. Zerumbone inhibits Helicobacter pylori urease activity. Molecules 26: 2663.
    Pubmed KoreaMed
  18. Choe D, Palsson B, Cho BK. 2020. STATR: A simple analysis pipeline of Ribo-Seq in bacteria. J. Microbiol. 58: 217-226.
    Pubmed KoreaMed
  19. Trapnell C, Williams BA, Pertea G, Mortazavi A, Kwan G, van Baren MJ, et al. 2010. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat. Biotechnol. 28: 511-515.
    Pubmed KoreaMed
  20. Trapnell C, Roberts A, Goff L, Pertea G, Kim D, Kelley DR, et al. 2012. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat. Protoc. 7:562-578.
    Pubmed KoreaMed
  21. Benjamini Y, Hochberg Y. 1995. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. Royal Stat. Soc.: Series B (Methodological) 57: 289-300.
  22. Campbell EA, Korzheva N, Mustaev A, Murakami K, Nair S, Goldfarb A, et al. 2001. Structural mechanism for rifampicin inhibition of bacterial rna polymerase. Cell 104: 901-912.
  23. Dailidiene D, Tan S, Ogura K, Zhang M, Lee AH, Severinov K, et al. 2007. Urea sensitization caused by separation of Helicobacter pylori RNA polymerase beta and beta' subunits. Helicobacter 12: 103-111.
    Pubmed
  24. Nitharwal RG, Verma V, Dasgupta S, Dhar SK. 2011. Helicobacter pylori chromosomal DNA replication: current status and future perspectives. FEBS Lett. 585: 7-17.
    Pubmed
  25. Goh KL, Chan WK, Shiota S, Yamaoka Y. 2011. Epidemiology of Helicobacter pylori infection and public health implications. Helicobacter 16 Suppl 1: 1-9.
    Pubmed KoreaMed
  26. Boquet P, Ricci V. 2012. Intoxication strategy of Helicobacter pylori VacA toxin. Trends Microbiol. 20: 165-174.
    Pubmed
  27. Fan E, Chauhan N, Udatha DB, Leo JC, Linke D. 2016. Type V secretion systems in bacteria. Microbiol. Spectr. 4. doi: 10.1128/microbiolspec.VMBF-0009-2015.
    Pubmed
  28. Allan E, Dorrell N, Foynes S, Anyim M, Wren BW. 2000. Mutational analysis of genes encoding the early flagellar components of Helicobacter pylori: evidence for transcriptional regulation of flagellin A biosynthesis. J. Bacteriol. 182: 5274-5277.
    Pubmed KoreaMed
  29. Schirm M, Soo EC, Aubry AJ, Austin J, Thibault P, Logan SM. 2003. Structural, genetic and functional characterization of the flagellin glycosylation process in Helicobacter pylori. Mol. Microbiol. 48: 1579-1592.
    Pubmed
  30. Tsang J, Hoover TR. 2015. Basal body structures differentially affect transcription of RpoN- and FliA-dependent flagellar genes in Helicobacter pylori. J. Bacteriol. 197: 1921-1930.
    Pubmed KoreaMed
  31. Kwok T, Zabler D, Urman S, Rohde M, Hartig R, Wessler S, et al. 2007. Helicobacter exploits integrin for type IV secretion and kinase activation. Nature 449: 862-866.
    Pubmed
  32. Merino E, Flores-Encarnacion M, Aguilar-Gutierrez GR. 2017. Functional interaction and structural characteristics of unique components of Helicobacter pylori T4SS. FEBS J. 284: 35403549.
    Pubmed
  33. Terradot L, Waksman G. 2011. Architecture of the Helicobacter pylori cag-type IV secretion system. FEBS J. 278: 1213-1222.
    Pubmed
  34. Olbermann P, Josenhans C, Moodley Y, Uhr M, Stamer C, Vauterin M, et al. 2010. A global overview of the genetic and functional diversity in the Helicobacter pylori cag pathogenicity island. PLoS Genet. 6: e1001069.
    Pubmed KoreaMed
  35. Woo HJ, Yang JY, Kwon HJ, Kim HW, Kim S-H, Kim J-B. 2021. Comparative transcriptome analysis of caryophyllene-treated Helicobacter pylori. Microbiol. Biotechnol. Lett. 49: 440-448.
  36. Woo HJ, Yang JY, Lee MH, Kim HW, Kwon HJ, Park M, et al. 2020. Inhibitory effects of β-caryophyllene on Helicobacter pylori infection in vitro and in vivo. Int. J. Mol. Sci. 21: 1008.
    Pubmed KoreaMed
  37. Kwon HJ, Lee MH, Kim HW, Yang JY, Woo HJ, Park M, et al. 2020. Riboflavin inhibits growth of Helicobacter pylori by down-regulation of polA and dnaB genes. Biomed. Sci. Lett. 26: 288-295.
  38. Tharmalingam N, Kim SH, Park M, Woo HJ, Kim HW, Yang JY, et al. 2014. Inhibitory effect of piperine on Helicobacter pylori growth and adhesion to gastric adenocarcinoma cells. Infect. Agent Cancer. 9: 43.
    Pubmed KoreaMed
  39. Boonjakuakul JK, Canfield DR, Solnick JV. 2005. Comparison of Helicobacter pylori virulence gene expression in vitro and in the rhesus macaque. Infect. Immun. 73: 4895-4904.
    Pubmed KoreaMed
  40. Niehues M, Stark T, Keller D, Hofmann T, Hensel A. 2011. Antiadhesion as a functional concept for prevention of pathogens: N-Phenylpropenoyl-L-amino acid amides as inhibitors of the Helicobacter pylori BabA outer membrane protein. Mol. Nutr. Food Res. 55: 1104-1117.
    Pubmed
  41. Kim SH, Park M, Woo H, Tharmalingam N, Lee G, Rhee KJ, et al. 2012. Inhibitory effects of anthocyanins on secretion of Helicobacter pylori CagA and VacA toxins. Int. J. Med. Sci. 9: 838-842.
    Pubmed KoreaMed
  42. Kim SH, Lee MH, Park M, Woo HJ, Kim YS, Tharmalingam N, et al. 2018. Regulatory effects of black rice extract on Helicobacter pylori infection‐induced apoptosis. Mol. Nutr Food Res. 62:1700586.
    Pubmed
  43. Lee MH Woo HJ, Park M, Moon C, Eom YB, Kim SH, Kim JB. 2016. Plumbagin inhibits expression of virulence factors and growth of Helicobacter pylori. Microbiol. Biotechnol. Lett. 44: 218-226.

Starts of Metrics

Share this article on :

  • mail

Related articles in MBL

Most KeyWord ?

What is Most Keyword?

  • It is most registrated keyword in articles at this journal during for 2 years.