Association Between Horizontal Gene Transfer and Adaptation of Gastric Human Pathogen Helicobacter pylori to the Host

  • Surekha Challa
  • Nageswara Rao Reddy Neelapu


Helicobacter pylori exhibit remarkable survival even in the vulnerable environments such as acidic, peristalsis, phagocytosis and oxidative stress. These stresses on the pathogen in the host induce damage of DNA in the pathogen. H. pylori acquired the ability to survive DNA damage by transformation-mediated recombination DNA repair. This repair mechanism helps the pathogen in successfully infecting the host. While many pathogens are competent for transformation only in certain environmental conditions such as starvation, H. pylori is competent throughout the growth. H. pylori may acquire the genetic material from the surrounding environment and contribute to evolution and genetic diversity. The mechanism in acquiring genetic material is ‘horizontal gene transfer’, the major contributing factor in the development of bacterial diversity. Horizontal gene transfer may help the pathogen H. pylori in acquiring antigenic determinants, genes of antibiotic resistance and virulence factors from other organisms to alter and influence pathogenicity. In this chapter, we review and discuss the association between horizontal gene transfer and adaptation of gastric human pathogen H. pylori to the host.


Antibiotics resistance Evolution Horizontal gene transfer H. pylori Macro-diversity Multidrug resistance Nickel-binding proteins Nickel transporter genes 



CS and NNR are grateful to GITAM (Deemed to be University) for providing necessary facilities to carry out the research work and for extending constant support.

Authors Contribution

CS and NNR initiated the review, participated in writing and revised the manuscript.

Conflict of Interest

The authors declare that there is no potential conflict of interest.


  1. Alm RA, Ling LS, Moir DT, King BL, Brown ED, Doig PC, Smith DR, Noonan B, Guild BC, deJonge BL, Carmel G, Tummino PJ, Caruso A, Uria-Nickelsen M, Mills DM, Ives C, Gibson R, Merberg D, Mills SD, Jiang Q, Taylor DE, Vovis GF, Trust TJ (1999) Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature 397:176–180CrossRefGoogle Scholar
  2. Ando TD, Israel A, Kusugami K, Blaser MJ (1999) HP0333, a member of the dprA family, is involved in natural transformation in Helicobacter pylori. J Bacteriol 181:5572–5580PubMedPubMedCentralGoogle Scholar
  3. Bardhan KD, Morton D, Perry MJ, Sanders DS, Morris P, Rowland A, Thompson M, Mitchell TR, Roberts PM (2001) Ranitidine bismuth citrate with clarithromycin alone or with metronidazole for the eradication of Helicobacter pylori. Aliment Pharmacol Ther 15(8):1199–1204CrossRefGoogle Scholar
  4. Bolor-Erdene M, Namdag B, Yamaoka Y, Jav S (2017) Antibiotic resistance of Helicobacter pylori in Mongolia. J Infect Dev Ctries 11:887–894CrossRefGoogle Scholar
  5. Boyanova L, Ilieva J, Gergova G, Spassova Z, Nikolov R, Davidkov L, Evstatiev I, Kamburov V, Katsarov N, Mitov I (2009) Evaluation of clinical and socio-demographic risk factors for antibacterial resistance of Helicobacter pylori in Bulgaria. J Med Microbiol 58:94–100CrossRefGoogle Scholar
  6. Campanale M, Nucera E, Ojetti V, Cesario V, Di Rienzo TA, D’Angelo G, Pecere S, Barbaro F, Gigante G, De Pasquale T, Rizzi A, Cammarota G, Schiavino D, Franceschi F, Gasbarrini A (2014) Nickel free-diet enhances the Helicobacter pylori eradication rate: a pilot study. Dig Dis Sci 59:1851–1855. 24595654. CrossRefPubMedGoogle Scholar
  7. Challa C, Neelapu NRR (2018) Quorum sensing in Helicobacter pylori: role of biofilm and its implications for antibiotic resistance and immune evasion. In: Veera Bramha Chari P (ed) Implication of quorum sensing system in biofilm formation and virulence. Springer Nature, Switzerland, pp 361–381Google Scholar
  8. Challa S, Mohana Sheela G, Neelapu NRR (2018) Understanding the bacterial biofilm resistance to antibiotics and immune evasion. In: Veera Bramha Chari P (ed) Implication of quorum sensing system in biofilm formation and virulence. Springer Nature, Switzerland, pp 369–381CrossRefGoogle Scholar
  9. Dorer MS, Fero J, Salama NR (2010) DNA damage triggers genetic exchange in Helicobacter pylori. PLoS Pathog 6:e1001026CrossRefGoogle Scholar
  10. Eppinger M, Baar C, Linz B, Raddatz G, Lanz C, Keller H, Morelli G, Gressmann H, Achtman M, Schuster SC (2006) Who ate whom? Adaptive Helicobacter genomic changes that accompanied a host jump from early humans to large felines. PLoS Genet 2:e120. CrossRefPubMedPubMedCentralGoogle Scholar
  11. Fernandez-Gonzalez E, Backert S (2014) DNA transfer in the gastric pathogen Helicobacter pylori. J Gastroenterol 49:594–604CrossRefGoogle Scholar
  12. Ferrero RL, Jenks PJ (2001) Invivo adaptation to the host. In: HLT M, Mendz GL, Hazell SL (eds) Helicobacter pylori: physiology and genetics, Chap. 46. ASM Press, Washington, DC. Google Scholar
  13. Fischer F, Robbe-Saule M, Turlin E, Mancuso F, Michel V, Richaud P, Veyrier FJ, De Reuse H, Vinella D (2016) Characterization in Helicobacter pylori of a nickel transporter essential for colonization that was acquired during evolution by gastric Helicobacter species. PLoS Pathog 12(12):e1006018. CrossRefPubMedPubMedCentralGoogle Scholar
  14. Gao W, Cheng H, Hu F, Li J, Wang L, Yang G, Xu L, Zheng X (2010) The evolution of Helicobacter pylori antibiotics resistance over 10 years in Beijing, China. Helicobacter 15:460–466CrossRefGoogle Scholar
  15. Garcia-Aljaro C, Balleste E, Muniesa M (2017) Beyond the canonical strategies of horizontal gene transfer in prokaryotes. Curr Opin Microbiol 38:95–105CrossRefGoogle Scholar
  16. Hofreuter D, Haas R (2002) Characterization of two cryptic Helicobacter pylori plasmids: a putative source for horizontal gene transfer and gene shuffling. J Bacteriol 184(10):2755–2766CrossRefGoogle Scholar
  17. Hofreuter D, Odenbreit S, Henke G, Haas R (1998) Natural competence for DNA transformation in Helicobacter pylori: identification and genetic characterization of the comB locus. Mol Microbiol 28:1027–1038CrossRefGoogle Scholar
  18. Hofreuter D, Odenbreit S, Haas R (2001) Natural transformation competence in Helicobacter pylori is mediated by the basic components of a type IV secretion system. Mol Microbiol 41:379–391CrossRefGoogle Scholar
  19. Huang YQ, Huang GR, Wu MH, Tang HY, Huang ZS, Zhou XH, Yu WQ, Su JW, Mo XQ, Chen BP, Zhao LJ (2015) Inhibitory effects of emodin, baicalin, schizandrin and berberine on hefA gene: treatment of Helicobacter pylori-induced multidrug resistance. World J Gastroenterol 21:4225CrossRefGoogle Scholar
  20. Kurtaran H, Uyar ME, Kasapoglu B, Turkay C, Yilmaz T, Akcay A, Kanbay M (2008) Role of Helicobacter pylori in pathogenesis of upper respiratory system diseases. J Natl Med Assoc 100:1224CrossRefGoogle Scholar
  21. Lee SM, Kim N, Kwon YH, Nam RH, Kim JM, Park JY, Lee YS, Lee DH (2018) Rdxa, frxa, and efflux pump in metronidazole-resistant Helicobacter pylori: their relation to clinical outcomes. J Gastroenterol Hepatol 33:681–688CrossRefGoogle Scholar
  22. Linz B, Windsor HM, Gajewski JP, Hake CM, Drautz DI, Schuster SC, Marshall BJ (2013) Helicobacter pylori genomic microevolution during naturally occurring transmission between adults. PLoS One 8(12):e82187. CrossRefPubMedPubMedCentralGoogle Scholar
  23. Lood R, Erturk G, Mattiasson B (2017) Revisiting antibiotic resistance spreading in wastewater treatment plants—bacteriophages as a much neglected potential transmission vehicle. Front Microbiol 8:2298CrossRefGoogle Scholar
  24. Mohana Sheela G, Prathyusha AMVN, Neelapu NRR, Bramhachari PV (2018) Intra and inter-species communication in microbes: living with complex and sociable neighbors. In: Veera Bramha Chari P (ed) Implication of quorum sensing system in biofilm formation and virulence. Springer Nature, Switzerland, pp 7–16CrossRefGoogle Scholar
  25. Nammi D, Srimath-Tirumala-Peddinti RCPK, Neelapu NRR (2016) Identification of drug targets in Helicobacter pylori by in silico analysis: possible therapeutic implications for gastric cancer. Curr Cancer Drug Targets 16:79–98CrossRefGoogle Scholar
  26. Nammi D, Yarla NS, Chubarev VN, Tarasov VV, Barreto GE, Pasupulati CAM, Aliev G, Neelapu NRR (2017) A systematic in-silico analysis of Helicobacter pylori pathogenic islands for identification of novel drug target candidates. Curr Genomics 18:450–465CrossRefGoogle Scholar
  27. Ndip RN, Malange Takang AE, Ojongokpoko JE, Luma HN, Malongue A, Akoachere JF, Ndip LM, MacMillan M, Weaver LT (2008) Helicobacter pylori isolates recovered from gastric biopsies of patients with gastroduodenal pathologies in Cameroon: current status of antibiogram. Tropical Med Int Health 13:848–854CrossRefGoogle Scholar
  28. Nedenskov-Sorensen P, Bukholm G, Bovre K (1990) Natural competence for genetic transformation in Campylobacter pylori. J Infect Dis 161:365–366CrossRefGoogle Scholar
  29. Neelapu RR (2018) Role and regulation of transcriptional factors in gastric cancer. In: Nagaraju GP, Bramhachari PV (eds) Role of transcription factors in gastrointestinal malignancies. Springer, Heidelberg, pp 107–130Google Scholar
  30. Neelapu NRR, Pavani T (2013) Identification of novel drug targets in HpB38, HpP12, HpG27, Hpshi470, HpSJM180 strains of Helicobacter pylori: an insilico approach for therapeutic intervention. Curr Drug Targets 14:601–611CrossRefGoogle Scholar
  31. Neelapu NRR, Srimath-Tirumala-Peddinti RCPK, Nammi D, Pasupuleti ACM (2013) New strategies and paradigm for drug target discovery: a special focus on infectious diseases tuberculosis, malaria, leishmaniasis, trypanosomiasis and gastritis. Infect Disord Drug Targets 13(5):352–364CrossRefGoogle Scholar
  32. Neelapu NRR, Nammi D, ACM P, Surekha C (2014) Helicobacter pylori induced gastric inflammation, ulcer, and cancer: a pathogenesis perspective. Interdiscip J Microinflammation 1:113Google Scholar
  33. Neelapu NRR, Mutha NVR, Akula S (2015) Identification of potential drug targets in Helicobacter pylori strain HPAG1 by in silico genome analysis. Infect Disord Drug Targets 15:106–117CrossRefGoogle Scholar
  34. Neelapu NRR, Nammi D, Pasupuleti AMC, Challa S (2016) Targets against Helicobacter pylori and other tumor-producing bacteria. In: Villa TG, Vinas M (eds) New weapons to control bacterial growth. Springer, Heidelberg, pp 239–279CrossRefGoogle Scholar
  35. Neelapu NRR, Titash D, Surekha C (2018) Quorum sensing and its role in agrobacterium mediated gene transfer. In: Chari PVB (ed) Implication of quorum sensing system in biofilm formation and virulence. Springer Nature, Switzerland, pp 259–275CrossRefGoogle Scholar
  36. O’Rourke EJ, Chevalier C, Pinto AV, Thiberge JM, Ielpi L, Labigne A, Radicella JP (2003) Pathogen DNA as target for host-generated oxidative stress: role for repair of bacterial DNA damage in Helicobacter pylori colonization. Proc Natl Acad Sci U S A 100:2789–2794CrossRefGoogle Scholar
  37. Osaki T, Hanawa T, Manzoku T, Fukuda M, Kawakami H, Suzuki H, Yamaguchi H, Yan X, Taguchi H, Kurata S, Kamiya S (2006) Mutation of luxS affects motility and infectivity of Helicobacter pylori in gastric mucosa of a mongolian gerbil model. J Med Microbiol 55:1477–1485CrossRefGoogle Scholar
  38. Pasupuleti AMP, Nammi D, Neelapu NRR (2017) Screening and identification of drug targets and vaccine candidates for Helicobacter pylori strain Hp26695. Int J Recent Sci Res 8(4):16384–16395CrossRefGoogle Scholar
  39. Pot RG, Kusters JG, Smeets LC, Van Tongeren W, Vandenbroucke-Grauls CM, Bart A (2001) Interspecies transfer of antibiotic resistance between Helicobacter pylori and Helicobacter acinonychis. Antimicrob Agents Chemother 45(10):2975–2976CrossRefGoogle Scholar
  40. Savarino V, Mansi C, Mele MR, Bisso G, Mela GS, Saggioro A, Caroli M, Vigneri S, Termini R, Olivieri A, Tosatto R, Celle G (1997) A new 1-week therapy for Helicobacter pylori eradication: ranitidine bismuth citrate plus two antibiotics. Aliment Pharmacol Ther 11(4):699–703CrossRefGoogle Scholar
  41. Schmitt W, Odenbreit S, Heuermann D, Haas R (1995) Cloning of the Helicobacter pylori recA gene and functional characterization of its product. Mol Gen Genet 248:563–572CrossRefGoogle Scholar
  42. Schuster SC, Wittekindt NE, Linz B (2008) Molecular mechanisms of host-adaptation in Helicobacter. In: Yamaoka Y (ed) Helicobacter pylori: molecular genetics and cellular biology. Horizon Scientific Press, Wymondham, pp 193–204Google Scholar
  43. Smeets LC, Bijlsma JJ, Boomkens SY, Vandenbroucke-Grauls CM, Kusters JG (2000) comH, a novel gene essential for natural transformation of Helicobacter pylori. J Bacteriol 182:3948–3954CrossRefGoogle Scholar
  44. Sun QJ, Liang X, Zheng Q, Gu WQ, Liu WZ, Xiao SD, Lu H (2010) Resistance of Helicobacter pylori to antibiotics from 2000 to 2009 in Shanghai. World J Gastroenterol 16:5118CrossRefGoogle Scholar
  45. Tomb JF, White O, Kerlavage AR, Clayton RA, Sutton GG, Fleischmann RD, Ketchum KA, Klenk HP, Gill S, Dougherty BA, Nelson K, Quackenbush J, Zhou L, Kirkness EF, Peterson S, Loftus B, Richardson D, Dodson R, Khalak HG, Glodek A, McKenney K, Fitzegerald LM, Lee N, Adams MD, Hickey EK, Berg DE, Gocayne JD, Utterback TR, Peterson JD, Kelley JM, Cotton MD, Weidman JM, Fujii C, Bowman C, Watthey L, Wallin E, Hayes WS, Borodovsky M, Karp PD, Smith HO, Fraser CM, Venter JC (1997) The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature 388:539–547CrossRefGoogle Scholar
  46. Torres J, Camorlinga-Ponce M, Pérez-Pérez G, Madrazo-De la Garza A, Dehesa M, González-Valencia G, Muñoz O (2001) Increasing multidrug resistance in Helicobacter pylori strains isolated from children and adults in Mexico. J Clin Microbiol 39:2677–2680CrossRefGoogle Scholar
  47. Vinella D, Fischer F, Vorontsov E, Gallaud J, Malosse C, Michel V, Cavazza C, Robbe-Saule M, Richaud P, Chamot-Rooke J, Brochier-Armanet C, De Reuse H (2015) Evolution of Helicobacter: acquisition by gastric species of two histidine-rich proteins essential for colonization. PLoS Pathog 11(12):e1005312. CrossRefPubMedPubMedCentralGoogle Scholar
  48. Von Wintersdorff CJ, Penders J, van Niekerk JM, Mills ND, Majumder S, van Alphen LB, Savelkoul PHM, Wolffs PFG (2016) Dissemination of antimicrobial resistance in microbial ecosystems through horizontal gene transfer. Front Microbiol 7:173Google Scholar
  49. Wang Y, Roos KP, Taylor DE (1993) Transformation of Helicobacter pylori by chromosomal metronidazole resistance and by a plasmid with a selectable chloramphenicol resistance marker. J Gen Microbiol 139:2485–2493CrossRefGoogle Scholar
  50. Wüppenhorst N, Lenze F, Ross M, Kist M (2011) Isolation and eradication of a clinical isolate of Helicobacter pylori resistant to five antimicrobials in Germany. J Antimicrob Chemother 66:222–223CrossRefGoogle Scholar
  51. Zullo A, De Francesco V, Hassan C, Morini S, Vaira D (2007) The sequential therapy regimen for Helicobacter pylori eradication: a pooled-data analysis. Gut 56(10):1353–1357CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Surekha Challa
    • 1
  • Nageswara Rao Reddy Neelapu
    • 1
  1. 1.Department of Biochemistry and Bioinformatics, Institute of ScienceGandhi Institute of Technology and Management (GITAM), Deemed to be UniversityVisakhapatnamIndia

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