Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 -- 1335 2024-05-15 11:34:28 |
2 format -9 word(s) 1326 2024-05-16 04:02:55 | |
3 Link to original paper added to the Description. + 9 word(s) 1335 2024-05-17 05:49:22 |

Video Upload Options

Do you have a full video?

Confirm

Are you sure to Delete?
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Taylor-Robinson, A.W.; Sedarat, Z. Helicobacter pylori infection, pathogenicity, and therapeutic advances. Encyclopedia. Available online: https://encyclopedia.pub/entry/56656 (accessed on 26 May 2024).
Taylor-Robinson AW, Sedarat Z. Helicobacter pylori infection, pathogenicity, and therapeutic advances. Encyclopedia. Available at: https://encyclopedia.pub/entry/56656. Accessed May 26, 2024.
Taylor-Robinson, Andrew W., Zahra Sedarat. "Helicobacter pylori infection, pathogenicity, and therapeutic advances" Encyclopedia, https://encyclopedia.pub/entry/56656 (accessed May 26, 2024).
Taylor-Robinson, A.W., & Sedarat, Z. (2024, May 15). Helicobacter pylori infection, pathogenicity, and therapeutic advances. In Encyclopedia. https://encyclopedia.pub/entry/56656
Taylor-Robinson, Andrew W. and Zahra Sedarat. "Helicobacter pylori infection, pathogenicity, and therapeutic advances." Encyclopedia. Web. 15 May, 2024.
Helicobacter pylori infection, pathogenicity, and therapeutic advances
Edit

A primer on Helicobacter pylori virulence factors, pathogenicity, gastric conditions that are caused by infection, and treatment modalities.

This entry is adapted from the peer-reviewed paper 10.3390/pathogens13050392

 Helicobacter pylori  virulence factor outer membrane protein gastric cancer gastric disease

1. Introduction

Helicobacter pylori is considered an ancient microorganism, the existence of which can be traced back to before the voyages of Christopher Columbus [1]. Yet, it took until the early 1980s for the bacterium to be first identified by the Australian physicians Barry Marshall and Robin Warren. For discovering H. pylori as the principal cause of gastritis, peptic ulcer disease and mucosa-associated lymphoid-tissue (MALT) lymphoma [2][3], they were awarded the Nobel Prize in Physiology or Medicine in 2005.

Chronic H. pylori infection is a predisposing factor for a range of other health conditions including ischemic stroke, Alzheimer’s disease, multiple sclerosis, autoimmune neutropenia, vitamin B12 deficiency, diabetes mellitus, cholelithiasis, idiopathic thrombocytopenic purpura, iron-deficiency anemia, cardiovascular diseases, hepatobiliary diseases, and biofilm-related infections, although further research is needed to verify each proposed link [4][5][6][7][8][9][10][11][12][13][14][15]. It is estimated that more than half of the world’s population is infected with this microorganism, its prevalence in developing countries reaching 70–90%, compared to developed nations where it is between 20–30% [16][17]. Typically, a person becomes infected with H. pylori during childhood through either oral–fecal or oral–oral routes of transmission [18].

This Gram-negative, microaerophilic, helical bacterium is a major source of global gastric cancer mortality, so it is considered as an oncogenic pathogen (oncopathogen) and hence is classified as a class I carcinogen by the World Health Organization [19]. It is equipped with different virulence factors including flagella, lipopolysaccharide (LPS), urease, and outer membrane proteins (OMPs), which are encoded by many paralogous gene families. It owes its characteristically high motility to its 4–6 co-located flagella, which facilitate its movement and colonization of the stomach mucosa layer. The first step for H. pylori to induce inflammation and cause infection is to colonize and attach to gastric mucosa. Usually, this happens through OMPs, which play a pivotal role in adherence and pathogenicity. To date, 64 members of this family have been recognized [20][21][22]. While some OMPs are porins, others are adhesins. Each OMP has a distinct receptor, so gaining a clear understanding of them all aids diagnosis of infection and benefits clinical outcomes.

Urease production provides ammonia for bacterial protein synthesis and neutralizes gastric acid, thereby making the stomach a preferred environment for colonization. This virulence factor can damage host tissue via several mechanisms, which, together with the inflammatory immune response that this triggers, causes ulceration. Similarly, the unique structure of LPS promotes bacterial pathogenicity by facilitating attachment to gastric mucosa, thus supporting persistence of infection [23][24][25][26].

Only around 20% of H. pylori carriers develop symptoms of disease. Chronic gastritis is the condition ascribed for H. pylori carriers without any clinical symptoms. At the same time, this pathogen is a risk factor for progression to gastric problems like peptic ulcers [27][28][29]. Chronic gastritis follows colonization of the stomach by H. pylori, which resists clearance and causes mucosal inflammation and atrophy. Peptic ulcer formation, a consequence of damaged mucosa through stomach acid activity, is accelerated by the chronically acidic environment [30]. These sores can develop either into a lesion inside the stomach, known as a gastric ulcer, or inside the adjoining duodenum within the small intestine, termed a duodenal ulcer [31]. Importantly, having chronic gastritis increases a person’s risk of acquiring severe gastric conditions, notably gastric cancer that most often manifests as stomach adenocarcinoma [32].

H. pylori is the leading cause of two-thirds of all stomach cancer and three-quarters of non-cardia gastric cancer (that affects the first part of the stomach) [33]. While there is now a decreasing trend in the rate of gastric cancer worldwide, it is still the second highest cause of cancer mortality [34]. The progression of H. pylori infection to gastric cancer happens through a series of events. Primary inflammation may develop into acute gastritis and chronic gastritis. At this stage, multiple factors such as stomach pH, genetic diversity and environmental factors can gradually alter the gastric condition to cancer.

Most patients are unaware of their condition during the early stages and so treatment is not started until symptoms are more advanced. Hence, developing earlier and more accurate screening methods to enable prevention and eradication of H. pylori at the community level, as well as better treatment strategies to combat existing infection in patients, are warranted [35]. An array of contributing factors, such as genetic susceptibility, diet, environmental variables, smoking and physical activity, are involved in progression to severe stomach conditions [36]. When considering these relationships as potential prognostic markers a number of challenges such as limited time of survival and geographical regionality of occurrence should be considered.

The protective host immune response to H. pylori helps to lessen the threat that colonization poses. However, this noted pathogen has evolved a unique strategy to overcome host defenses. Long-term infection is a consequence of remodeling of the host-pathogen interface as well as immune evasion due to expression of multiple virulence factors [37]. Hence, through modulating host immunity and inducing immune tolerance, H. pylori hinders therapeutic approaches and effective vaccine design.

In order to eradicate H. pylori, antibiotics are suggested for gastric disorders. These are often used in combination with proton pump inhibitors as a standard intervention [38]. However, a challenge to effective therapy is the capacity of H. pylori to form biofilm. Under the protection of the impervious matrix of extracellular polymeric substances (EPS), bacteria are refractory to antibiotic penetration, thus greatly reducing the efficacy of this treatment approach [39]. There is strong evidence for a direct correlation between biofilm formation and antibiotic resistance, influenced by factors such as OMPs, other virulence factors, extracellular matrix, efflux pumps and metabolic changes [40]. Therefore, susceptibility to antibiotics such as amoxicillin, clarithromycin, levofloxacin, and metronidazole by bacteria protected by biofilm is reduced substantially [41]. It should also be noted that eradicating this microorganism may provoke extra-gastric diseases, in particular iron deficiency, idiopathic thrombocytopenic purpura, chronic idiopathic urticaria and anemia. Further studies are required to confirm this correlation [42].

With the rise of antibiotic-resistant strains of H. pylori, there is a growing emphasis on exploring alternative treatments to antibiotics. Consequently, the development of an H. pylori vaccine has been extensively researched. Two types of vaccine, whole-cell bacterium and a recombinant preparation, which combines protective antigens with immune adjuvants, are considered the main approaches [43]. While development of the former was abandoned for various reasons, including complexity of vaccine production, the latter has progressed extensively. Different immune adjuvants, including the virulence factors BabA, SabA, OipA, CagA, and VacA, have provided vaccines with higher protective effects [44]. Four highly conserved OMPs were discovered that offer considerable potential as vaccine candidates. These proteins, namely HopV, HopW, HopX, and HopY, show no signs of phase variation, indicating stable expression during chronic infection and thereby their suitability as immunogens [44][45].

Yet, despite almost 40 years of research and development, no H. pylori vaccine is commercially available, with most clinical trials concluding after phase I. In addition to genetic diversity, biofilm characteristics, and the risk of exacerbating gastric diseases and autoimmunity due to an aberrant immune response, other reasons may partly account for this. For example, intracellular features of H. pylori enable it to effectively ‘hide’ inside gastric epithelial cells and gastric lamina propria, thus contributing to persistent infection [46]. Another concern is that many preclinical studies have been performed in mice, which are not natural hosts of H. pylori. Hence, any vaccine efficacy observed in mouse models may not translate accurately to humans [47]. Enhancing investment and prioritizing research into the design of an efficacious H. pylori vaccine are public health imperatives considering the widespread prevalence and significant disease burden associated with this bacterium.

Regarding other therapeutic approaches directly against H. pylori, several targets are suggested for treatment. These include shikimate pathways (involved in ubiquinone and aromatic acid synthesis), flavodoxin (electron carrier protein), coenzyme A, succinylase pathway, and urease inhibitory compounds. By developing reagents that interfere with these targets, researchers aim to disrupt essential bacterial functions and reduce colonization by H. pylori, leading to its control or even eradication from within the host [48].

References

  1. Yoshio Yamaoka; Etsuro Orito; Masashi Mizokami; Oscar Gutierrez; Naruya Saitou; Tadashi Kodama; Michael S Osato; Jong G Kim; Francisco C Ramirez; Varocha Mahachai; David Y Graham; Helicobacter pylori in North and South America before Columbus. FEBS Lett.. 2002, 517, 180-184.
  2. Geoff Watts; Nobel prize is awarded to doctors who discovered H pylori. BMJ. 2005, 331, 795.1-795.
  3. Michael Höcker; Peter Hohenberger; Helicobacter pylori virulence factors—one part of a big picture. Lancet. 2003, 362, 1231-1233.
  4. Di Zhou; Yong Zhang; Wei Gong; Sayid Omar Mohamed; Henry Ogbomo; Xuefeng Wang; Yingbin Liu; Zhiwei Quan; Are Helicobacter Pylori and Other Helicobacter Species Infection Associated with Human Biliary Lithiasis? A Meta-Analysis. PLOS ONE. 2011, 6, e27390.
  5. Hideo Yonezawa; Takako Osaki; Timothy Woo; Satoshi Kurata; Cynthia Zaman; Fuhito Hojo; Tomoko Hanawa; Shuichi Kato; Shigeru Kamiya; Analysis of outer membrane vesicle protein involved in biofilm formation of Helicobacter pylori. Anaerobe. 2011, 17, 388-390.
  6. Antonietta Gerarda Gravina; Rocco Maurizio Zagari; Cristiana De Musis; Lorenzo Romano; Carmelina Loguercio; Marco Romano; Helicobacter pylori and extragastric diseases: A review. World J. Gastroenterol.. 2018, 24, 3204-3221.
  7. G. Capurso; E. Lahner; A. Marcheggiano; P. Caruana; A. Carnuccio; C. Bordi; G. Delle Fave; B. Annibale; Involvement of the corporal mucosa and related changes in gastric acid secretion characterize patients with iron deficiency anaemia associated with Helicobacter pylori infection. Aliment. Pharmacol. Ther.. 2001, 15, 1753-1761.
  8. Rinaldo Pellicano; Francesco Franceschi; Giorgio Saracco; Sharmila Fagoonee; Davide Roccarina; Antonio Gasbarrini; Helicobacters and Extragastric Diseases. Helicobacter. 2009, 14, 58-68.
  9. D. M. Arnold; A. Bernotas; I. Nazi; R. Stasi; M. Kuwana; Y. Liu; J. G. Kelton; M. A. Crowther; Platelet count response to H. pylori treatment in patients with immune thrombocytopenic purpura with and without H. pylori infection: a systematic review. Haematol.. 2009, 94, 850-856.
  10. Tahereh Pirouz; Leila Zounubi; Hussein Keivani; Nasser Rakhshani; Mahshid Hormazdi; Detection of Helicobacter pylori in Paraffin-Embedded Specimens from Patients with Chronic Liver Diseases, Using the Amplification Method. Dig. Dis. Sci.. 2008, 54, 1456-1459.
  11. Xiaoying Zhou; Cuiling Zhang; Junbei Wu; Guoxin Zhang; Association between Helicobacter pylori infection and diabetes mellitus: A meta-analysis of observational studies. Diabetes Res. Clin. Pr.. 2013, 99, 200-208.
  12. Dong Wook Shin; Hyuk Tae Kwon; Jung Min Kang; Jin Ho Park; Ho Chun Choi; Min Seon Park; Sang Min Park; Ki Young Son; BeLong Cho; Association Between Metabolic Syndrome and Helicobacter pylori Infection Diagnosed by Histologic Status and Serological Status. J. Clin. Gastroenterol.. 2012, 46, 840-845.
  13. Rajesh Vijayvergiya; Role ofHelicobacter pyloriinfection in pathogenesis of atherosclerosis. World J. Cardiol.. 2015, 7, 134-43.
  14. Hiroyuki Osawa; Masanobu Kawakami; Mikihisa Fujii; Norifumi Kubo; Hisakazu Iwanaka; Wari Yamamoto; Muneyasu Saitoh; Toshio Yaginuma; Kentaro Sugano; Helicobacter pylori Infection and Coronary Heart Disease in Japanese Patients. Cardiol.. 2001, 95, 14-19.
  15. Xiong‐Zhi Wu; Dan Chen; Helicobacter pylori and hepatocellular carcinoma: Correlated or uncorrelated?. J. Gastroenterol. Hepatol.. 2006, 21, 345-347.
  16. James K.Y. Hooi; Wan Ying Lai; Wee Khoon Ng; Michael M.Y. Suen; Fox E. Underwood; Divine Tanyingoh; Peter Malfertheiner; David Y. Graham; Vincent W.S. Wong; Justin C.Y. Wu; Francis K.L. Chan; Joseph J.Y. Sung; Gilaad G. Kaplan; Siew C. Ng; Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology. 2017, 153, 420-429.
  17. 17. Dunn, B.E.; Cohen, H.; Blaser, M.J. Helicobacter pylori. Clin. Microbiol. Rev.. 1997, 10, 720-741.
  18. Khean‐Lee Goh; Wah‐Kheong Chan; Seiji Shiota; Yoshio Yamaoka; Epidemiology of Helicobacter pylori Infection and Public Health Implications. Helicobacter. 2011, 16, 1-9.
  19. D. Max Parkin; Freddie Bray; J. Ferlay; Paola Pisani; Global Cancer Statistics, 2002. CA: A Cancer J. Clin.. 2005, 55, 74-108.
  20. Janaki L. Guruge; Per G. Falk; Robin G. Lorenz; Maria Dans; Hans-Peter Wirth; Martin J. Blaser; Douglas E. Berg; Jeffrey I. Gordon; Epithelial attachment alters the outcome of Helicobacter pylori infection. Proc. Natl. Acad. Sci.. 1998, 95, 3925-3930.
  21. Jean-F. Tomb; Owen White; Anthony R. Kerlavage; Rebecca A. Clayton; Granger G. Sutton; Robert D. Fleischmann; Karen A. Ketchum; Hans Peter Klenk; Steven Gill; Brian A. Dougherty; Karen Nelson; John Quackenbush; Lixin Zhou; Ewen F. Kirkness; Scott Peterson; Brendan Loftus; Delwood Richardson; Robert Dodson; Hanif G. Khalak; Anna Glodek; Keith McKenney; Lisa M. Fitzegerald; Norman Lee; Mark D. Adams; Erin K. Hickey; Douglas E. Berg; Jeanine D. Gocayne; Teresa R. Utterback; Jeremy D. Peterson; Jenny M. Kelley; Matthew D. Cotton; Janice M. Weidman; Claire Fujii; Cheryl Bowman; Larry Watthey; Erik Wallin; William S. Hayes; Mark Borodovsky; Peter D. Karp; Hamilton O. Smith; Claire M. Fraser; J. Craig Venter; The complete genome sequence of the gastric pathogen Helicobacter pylori. Nat.. 1997, 388, 539-547.
  22. Richard A. Alm; James Bina; Beth M. Andrews; Peter Doig; Robert E. W. Hancock; Trevor J. Trust; Comparative Genomics ofHelicobacter pylori: Analysis of the Outer Membrane Protein Families. Infect. Immun.. 2000, 68, 4155-4168.
  23. Shi-He Shao; Hua Wang; Shun-Gen Chai; Li-Mei Liu; Research progress onHelicobacter pyloriouter membrane protein. World J. Gastroenterol.. 2005, 11, 3011-3013.
  24. AP Moran; The role of lipopolysaccharide in Helicobacter pylori pathogenesis.. Aliment. Pharmacol. Ther.. 1996, 10, 39-50.
  25. Haiying Gu; Role of Flagella in the Pathogenesis of Helicobacter pylori. Curr. Microbiol.. 2017, 74, 863-869.
  26. Hl Mobley; The role of Helicobacter pylori urease in the pathogenesis of gastritis and peptic ulceration.. Aliment. Pharmacol. Ther.. 1996, 10, 57-64.
  27. Enno Hentschel; Gerald Brandstatter; Brigitte Dragosics; Alexander M. Hirschl; Heinz Nemec; Kurt Schutze; Margareta Taufer; Herbert Wurzer; Effect of Ranitidine and Amoxicillin plus Metronidazole on the Eradication of Helicobacter pylori and the Recurrence of Duodenal Ulcer. New Engl. J. Med.. 1993, 328, 308-312.
  28. Michal Sibony; Nicola L. Jones; Recent advances in Helicobacter pylori pathogenesis. Curr. Opin. Gastroenterol.. 2012, 28, 30-35.
  29. Yoshio Yamaoka; Roles of the plasticity regions of Helicobacter pylori in gastroduodenal pathogenesis. J. Med Microbiol.. 2008, 57, 545-553.
  30. Motohiro Kobayashi; Heeseob Lee; Jun Nakayama; Minoru Fukuda; Roles of gastric mucin-type O-glycans in the pathogenesis of Helicobacter pylori infection. Glycobiol.. 2009, 19, 453-461.
  31. Lucija Kuna; Jelena Jakab; Robert Smolic; Nikola Raguz-Lucic; Aleksandar Vcev; Martina Smolic; Peptic Ulcer Disease: A Brief Review of Conventional Therapy and Herbal Treatment Options. J. Clin. Med.. 2019, 8, 179.
  32. Pekka Laurén; The two histological main types of gastric carcinoma: Diffuse and so-called intestinal-type carcinoma. An attempt at histo-clinical classification. Acta Pathol. Microbiol. Scand. 1965, 64, 31-49.
  33. Donald Maxwell Parkin; The global health burden of infection‐associated cancers in the year 2002. Int. J. Cancer. 2006, 118, 3030-3044.
  34. Jacques Ferlay; Hai‐Rim Shin; Freddie Bray; David Forman; Colin Mathers; Donald Maxwell Parkin; Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int. J. Cancer. 2010, 127, 2893-2917.
  35. P Correa; Is gastric cancer preventable?. Gut. 2004, 53, 1217-1219.
  36. D. Forman; V.J. Burley; Gastric cancer: global pattern of the disease and an overview of environmental risk factors. Best Pr. Res. Clin. Gastroenterol.. 2006, 20, 633-649.
  37. Akriti Prashar; Mariana I. Capurro; Nicola L. Jones; Under the Radar: Strategies Used by Helicobacter pylori to Evade Host Responses. Annu. Rev. Physiol.. 2022, 84, 485-506.
  38. Vasilios Papastergiou; Sotirios D Georgopoulos; Stylianos Karatapanis; Treatment ofHelicobacter pyloriinfection: Meeting the challenge of antimicrobial resistance. World J. Gastroenterol.. 2014, 20, 9898-911.
  39. G. Cammarota; M. Sanguinetti; A. Gallo; B. Posteraro; Review article: biofilm formation by Helicobacter pylori as a target for eradication of resistant infection. Aliment. Pharmacol. Ther.. 2012, 36, 222-230.
  40. Yasmine Elshenawi; Shuai Hu; Skander Hathroubi; Biofilm of Helicobacter pylori: Life Cycle, Features, and Treatment Options. Antibiot.. 2023, 12, 1260.
  41. Kartika Afrida Fauzia; Muhammad Miftahussurur; Ari Fahrial Syam; Langgeng Agung Waskito; Dalla Doohan; Yudith Annisa Ayu Rezkitha; Takashi Matsumoto; Vo Phuoc Tuan; Junko Akada; Hideo Yonezawa; Shigeru Kamiya; Yoshio Yamaoka; Biofilm Formation and Antibiotic Resistance Phenotype of Helicobacter pylori Clinical Isolates. Toxins. 2020, 12, 473.
  42. Karen J. Goodman; Stephanie L. Joyce; Kathleen P. Ismond; Extragastric diseases associated with Helicobacter pylori infection. Curr. Gastroenterol. Rep.. 2006, 8, 458-464.
  43. Carlo A. Fallone; Steven F. Moss; Peter Malfertheiner; Reconciliation of Recent Helicobacter pylori Treatment Guidelines in a Time of Increasing Resistance to Antibiotics. Gastroenterology. 2019, 157, 44-53.
  44. Chenjing Xu; Djaleel Muhammad Soyfoo; Yao Wu; Shunfu Xu; Virulence of Helicobacter pylori outer membrane proteins: an updated review. Eur. J. Clin. Microbiol. Infect. Dis.. 2020, 39, 1821-1830.
  45. Birgit Peck; Martina Ortkamp; Uwe Nau; Michael Niederweis; Erika Hundt; Bernhard Knapp; Characterization of four members of a multigene family encoding outer membrane proteins of Helicobacter pylori and their potential for vaccination. Microbes Infect.. 2001, 3, 171-179.
  46. Vittorio Necchi; Maria Elena Candusso; Francesca Tava; Ombretta Luinetti; Ulderico Ventura; Roberto Fiocca; Vittorio Ricci; Enrico Solcia; Intracellular, Intercellular, and Stromal Invasion of Gastric Mucosa, Preneoplastic Lesions, and Cancer by Helicobacter pylori. Gastroenterology. 2007, 132, 1009-1023.
  47. Hadi Maleki Kakelar; Abolfazl Barzegari; Jaber Dehghani; Shahram Hanifian; Nazli Saeedi; Jaleh Barar; Yadollah Omidi; Pathogenicity of Helicobacter pylori in cancer development and impacts of vaccination. Gastric Cancer. 2018, 22, 23-36.
  48. Ayla Debraekeleer; Han Remaut; Future perspective for potential Helicobacter pylori eradication therapies. Futur. Microbiol.. 2018, 13, 671-687.
More
Information
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : ,
View Times: 206
Entry Collection: Common Diseases
Revisions: 3 times (View History)
Update Date: 17 May 2024
1000/1000
Video Production Service