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
Judeng Zeng
 -- 2401 2022-10-17 11:33:02 |
2 format correct
Vivi Li
 + 32 word(s) 2433 2022-10-18 03:45:38 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Zeng, J.;  Xie, C.;  Zhang, L.;  Liu, X.;  Chan, M.T.V.;  Wu, W.K.K.;  Chen, H. Host Cell Antimicrobial Responses against Helicobacter pylori Infection. Encyclopedia. Available online: https://encyclopedia.pub/entry/29682 (accessed on 02 July 2024).
Zeng J,  Xie C,  Zhang L,  Liu X,  Chan MTV,  Wu WKK, et al. Host Cell Antimicrobial Responses against Helicobacter pylori Infection. Encyclopedia. Available at: https://encyclopedia.pub/entry/29682. Accessed July 02, 2024.
Zeng, Judeng, Chuan Xie, Lin Zhang, Xiaodong Liu, Matthew Tak Vai Chan, William Ka Kei Wu, Huarong Chen. "Host Cell Antimicrobial Responses against Helicobacter pylori Infection" Encyclopedia, https://encyclopedia.pub/entry/29682 (accessed July 02, 2024).
Zeng, J.,  Xie, C.,  Zhang, L.,  Liu, X.,  Chan, M.T.V.,  Wu, W.K.K., & Chen, H. (2022, October 17). Host Cell Antimicrobial Responses against Helicobacter pylori Infection. In Encyclopedia. https://encyclopedia.pub/entry/29682
Zeng, Judeng, et al. "Host Cell Antimicrobial Responses against Helicobacter pylori Infection." Encyclopedia. Web. 17 October, 2022.
Host Cell Antimicrobial Responses against Helicobacter pylori Infection
Edit
This entry is adapted from the peer-reviewed paper 10.3390/ijms231810941

The colonization of Helicobacter pylori (H. pylori) in human gastric mucosa is highly associated with the occurrence of gastritis, peptic ulcer, and gastric cancer. Antibiotics, including amoxicillin, clarithromycin, furazolidone, levofloxacin, metronidazole, and tetracycline, are commonly used and considered the major treatment regimens for H. pylori eradication. Evidence has pointed out that a small portion of H. pylori can invade and replicate in the intracellular compartments of different cell types, causing persistent infection by evading host immune defense and antibiotics. Under this circumstance, host cells have developed numerous antimicrobial responses to fight against invading H. pylori, e.g., induction of antimicrobial peptides, activation of cellular autophagy pathway, and increased oxidative stress.

helicobacter pylori host cells antimicrobial responses antibiotic-resistance

1. Introduction

Gram-negative, microaerophilic, spiral-shaped Helicobacter pylori (H. pylori) is commonly identified in the stomach. It has been reported to infect more than a half of the world’s population and can persist life-long without eradication [1][2]. The H. pylori infection is thought to occur during childhood within families by the oral-oral or fecal-oral route, with a higher prevalence in developing countries probably due to poor hygiene and crowded conditions [3]. The H. pylori infection is a risk factor for chronic gastritis and peptic ulcer and recognized as a class I carcinogen of gastric cancer by the World Health Organization (WHO) [4].
The successful colonization and pathogenesis of H. pylori are owing to the action of a variety of bacterial virulence factors. On the one hand, H. pylori can generate numerous ureases to neutralize the acidic environment of the stomach lumen. On the other hand, the bacterial flagellar-dependent motility enables H. pylori to penetrate the mucus layer toward the gastric epithelium, where the pH is almost neutral [5]. Moreover, a variety of outer membrane proteins (OMPs) of the bacterium serve as adhesins that mediate the adherence of H. pylori to the surface of gastric epithelial cells [6]. The colonized H. pylori then produce numerous virulence factors, including two well-known cytotoxins-cytotoxic associated gene A (CagA) and vacuolating cytotoxin A (VacA), which can modulate the biological function of gastric epithelial cells and induce the release of proinflammatory cytokines to cause chronic inflammation [7]. For a long time, H. pylori was thought to be a non-invasive bacterium that mainly lived in the mucus layer [8]. However, current evidence has pointed out that a small portion of H. pylori can invade and replicate in the intracellular compartments of different cell types [9], causing persistent infection by evading host immune defense and antibiotics [10]. Under this circumstance, host cells have developed numerous antimicrobial responses to fight against invading H. pylori, e.g., induction of antimicrobial peptides [11][12], activation of cellular autophagy pathway [13], and increased oxidative stress [14].

2. Virulence Factors of H. pylori

The virulence factors of H. pylori are associated with bacterial colonization and the development of gastroduodenal diseases. Here, researchers briefly introduce some well-known bacterial adhesins and cytotoxins which are involved in host cell-bacterial interaction and pathogenesis.

2.1. Adhesins of H. pylori

The adhesion of H. pylori to the gastric epithelium is not only crucial for successful colonization and pathogenesis but also essential for invasion into host cells. Numerous studies have revealed that H. pylori expresses a variety of adhesion factors that could bind to related cell surface molecules, such as sugars or proteins. More than 30 H. pylori outer membrane proteins (OMPs) have been identified, which play pivotal roles in bacterial attachment to the gastric mucosa. These OMPs could be divided into two groups: Hop (Helicobacter outer membrane proteins) and Hor (Hop-related proteins) subgroups [15][16]. Below, researchers introduce several members of the Hop-family.

2.1.1. BabA

Blood group antigen-binding adhesin A (BabA) is a major adhesin of H. pylori. BabA mediates the adhesion of bacterium to the Lewis b blood group antigen (Leb), a major antigen expressed by gastric mucosa [17]. BabA could also bind to salivary mucin MUC5B, gastric mucin MUC5AC, etc. [18][19][20]. It has been reported that BabA-mediated H. pylori adherence to Leb on the gastric epithelium promoted type IV secretion system (T4SS) activity, resulting in the production of pro-inflammatory cytokines and other factors that contributed to the development of gastric tumorigenesis [21].

2.2. Cytotoxin-Associated Gene A (CagA) and Type IV Secretion System (T4SS)

Cytotoxin-associated gene A (CagA), the most well-studied virulence factor of H. pylori, is a 120–145-kDa immunogenic protein encoded in a 40-kb bacterial genomic DNA region known as cag pathogenicity island (cagPAI) [22]. Presumably, ~31 genes are located in this region and encode proteins of type IV secretion system (T4SS), which is deployed by H. pylori to deliver macromolecules into other bacteria or cells [23]. Based on the ability to produce CagA, H. pylori can be further classified as CagA-positive and -negative strains [24]. Approximately 30–40% of H. pylori strains isolated in Western countries (e.g., America, Australia) are CagA-negative which are less associated with the occurrence of peptic ulcer and gastric carcinogenesis, whereas almost all H. pylori strains isolated in East Asian countries (i.e., China, Japan, Korea) are CagA-positive with stronger pathogenicity [25].
CagA shows a highly polymorphic Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region [26]. Accumulating studies have shown that tyrosine phosphorylation in EPIYA motif plays an important role in the cytotoxicity of CagA. H. pylori could use T4SS apparatus to translocate CagA into host cells where the tyrosine within EPIYA motif of CagA are phosphorylated by c-Src and c-Abl tyrosine-protein kinases, resulting in disturbed cell signaling pathways and enhanced tumorigenesis [27][28]. In addition, non-phosphorylated CagA was also reported to impair the cellular signal transduction system [29]. It is reported that H. pylori CagA could induce epithelial-mesenchymal transition (EMT) in gastric cancer by activating YAP pathway [30]. Another study showed that CagA-positive H. pylori promoted DNA damage in gastric cancer via downregulating DNA repair protein Rad51 [31].

2.3. Vacuolating Cytotoxin A (VacA)

Vacuolating cytotoxin (VacA) is a secreted toxin encoded by H. pylori gene VacA, which is characterized by its ability to form pores and cause vacuolation in cultured eukaryotic cells [32]. VacA is initially produced as a 140-kDa pro-toxin, which is subjected to proteolytic cleavage to yield an active toxin of 88-kDa. Active VacA is secreted extracellularly and undergoes proteolysis to generate two fragments [33] (p. 33 and p. 55). The p. 33 contains a hydrophobic domain and is responsible for pore formation, while p. 55 contains a cell membrane-binding domain and mediates the internalization of VacA [32]. Besides, several VacA-binding receptors were identified at gastric epithelial cell surface, including epidermal growth factor (EGF) [34], receptor protein tyrosine phosphatase alpha/beta (RPTPα/β) [35][36], and low-density lipoprotein receptor-related protein-1 (LRP1) [37]. The internalized VacA exerts a variety of cytotoxic effects, e.g., forming chloride ion channels on late endosomes to induce vacuolation [38], trafficking to mitochondria to induce cytochrome c release and Bax/Bak-dependent apoptosis [39], and inducing autophagy with a reduced autophagic flux [40].
All H. pylori strains contain functional but highly variant VacA gene. The different combination of N-terminal “s” region (s1a, s1b, s1c and s2), “m” region (m1, m2) and the intermediate region (i1, i2) determine the pore-forming ability and pathogenicity of VacA [41]. It has been reported that VacA of s1/m1 genotype exhibits the highest vacuolating ability in vitro and is highly associated with the occurrence of gastrointestinal diseases. In contrast, s1/m2 genotype has an intermediate activity while s2/m2 genotype presents almost no cytotoxic activity [42][43]. Interestingly, almost all CagA-positive strains carry s1/m1 VacA while CagA-negative strains are usually s2/m2 genotype [43].

3. Host Cell Antimicrobial Responses against H. pylori Infection

The successful colonization of H. pylori results in chronic inflammation and the related pathogenesis in stomach. Meanwhile, host cells also develop numerous antimicrobial responses to defend against H. pylori infection. Here, researchers describe some innate defense strategies exploited by host cells, especially for gastric epithelial cells and professional phagocytic cells, to fight against invading H. pylori, including induction of antimicrobial peptides, activation of cellular autophagy pathway, and increased oxidative stress.

3.1. Antimicrobial Peptides

Antimicrobial peptides (AMPs), also called host defense peptides (HDPs), are a kind of biologically active small peptides that are widely expressed in almost all living organisms and serve as an important part of the innate immune system to protect the host against a wide spectrum of pathogens [44]. Most AMPs share some common features: (1) The number of amino acids is between 10 and 60, (2) they are cationic and amphipathic and can directly interact with negatively charged bacterial cell membrane to induce pore formation, membrane collapse, and content outflow, (3) they exert immunomodulatory functions, such as induction of pro-inflammatory cytokine release, modulation of the antigen presentation of dendritic cells, and activation of adaptive immune cells [45][46]. Upon H. pylori infection, human immune and epithelial cells can produce two major AMPs, cathelicidin/LL-37, and defensins, to protect the host against invading pathogens [47].

3.1.1. Cathelicidin/LL-37

As a part of the human innate immune system, cathelicidins are present in a variety of human tissues and organs [48]. Circulating neutrophil, macrophage, as well as epithelial cells of the skin and digestive tract, all express high levels of cathelicidins. In humans, the cathelicidin antimicrobial peptide (CAMP) gene encodes the peptide precursor human cationic antimicrobial peptide-18 (hCAP-18), which is then subject to C-terminal cleavage by extracellular serine proteinase-3 to generate active form of LL-37 [49]. LL-37 is the only member of the Cathelicidin family identified in humans. H. pylori infection can markedly induce both RNA and protein expression of LL-37 in the gastric epithelium in a T4SS-dependent manner [50]. Mechanically, the mechanistic target of rapamycin complex 1 (mTORC1) was activated in CagA-dependent manner to promote LL-37 expression upon H. pylori infection [51]. Activated LL-37 exerted a strong inhibitory effect against H. pylori and reduced H. pylori colonization in both in vitro gastric epithelial cell line model [52] and in vivo mouse model of gastritis [53]. Due to cationic and amphipathic structural features, LL-37 can rapidly disrupt cell membranes to induce pore formation of the bacteria [54] and further inhibit the formation of bacterial biofilm [55]. In addition to direct killing of microorganisms, LL-37 also exerted an immunomodulatory function by recruiting activated immune cells to infected sites to eliminate the invading bacteria [56][57].

3.1.2. Defensins

Defensins are cysteine-rich cationic AMPs regarded as a part of host innate immune systems to fight against bacterial infection [58]. α-defensin and β-defensin are two major subgroups of defensins in humans, which are widely expressed in immune and epithelial cells [59]. Six members of α-defensin have been identified in humans: Human neutrophil proteins 1 to 4 (HNP1–4) and human defensins 5 and 6 (HD5 and 6), which are secreted by granulocytes and Paneth cells, respectively [60]. H. pylori infection was reported to increase HNP1–3 levels in gastric juice and promote the release of active peptides from granulocytes. However, the exact mechanisms of H. pylori-induced α-defensin are still unclear [61][62]. On the other hand, more than 50 genes encoding β-defensins (HBDs) have been discovered, which are mainly produced by epithelial tissues. Among them, the roles of HBD1–4 in controlling bacterial infections have been widely studied [60]. HBD1 is constitutively expressed in gastric epithelial cells. The level of HBD1 was moderately increased during H. pylori infection [63][64]. Intriguingly, H. pylori-induced NLRC4 inflammasome was reported to activate IL-18 to inhibit HBD1 expression in an NF-κB-dependent manner [65]. In contrast, HBD2 expression was markedly elevated upon challenging with cag pathogenicity island positive (cagPAI+) H. pylori. Mechanically, internalization of bacterial peptidoglycan caused by cagPAI is recognized by nucleotide-binding oligomerization domain-1 (NOD1), resulting in induction of HBD2 [12]. In addition, HBD3 is induced upon H. pylori infection via a TAK1 (transforming growth factor β-activated kinase-1)-EGFR (epidermal growth factor receptor)-p38α axis, which is dependent on the type IV secretion system but independent of CagA or NOD1 [66]. Moreover, CagA-positive strains markedly increased HBD4 expression mediated by p38 [67]. Similar to LL-37, β-defensins exert antimicrobial activity mainly by permeabilizing the bacterial membrane [68]. Furthermore, β-defensins are chemotactic for immune cells, thereby controlling the host immune response to fight against invading H. pylori [60].

3.2. Autophagy Pathway

Autophagy is thought to be the original form of innate immune response of eukaryotic cells against intracellular microorganisms [69]. Besides, previous studies have reported that H. pylori could invade the gastric epithelial cells to cause persistent infection [70][71]. The interaction between cellular autophagy and bacterial factors determined the fate of intracellular H. pylori [72].

3.2.1. The Definition of Autophagy

“Autophagy” (the Greek word means “self-eating”) refers to cellular machinery that degrades unnecessary and dysfunctional intracellular components through a lysosome-dependent manner [73]. It allows the recycling of cytosolic materials and provides energy to support normal cell activities [74]. Autophagy is induced in response to different kinds of stress, including fasting, nutrient deprivation, infection, and hypoxia, to maintain cellular homeostasis and promote cell survival under harsh conditions. Although autophagy was initially considered a non-selective process, recent studies have pointed out that autophagy could eliminate some unwarned or harmful cytosolic materials, e.g., damaged mitochondria and invaded bacteria, in a selective manner [75]. There are three well-characterized types of autophagy: Macro-autophagy, micro-autophagy, and chaperone-mediated autophagy (CMA). For macro-autophagy, a double-membrane vesicle named autophagosome encloses cytosolic cargos, and then fuses with lysosome to form autolysosome where the cargos are degraded by the hydrolytic enzymes. Macro-autophagy is an important host cell defense mechanism against intracellular H. pylori [72].

3.2.2. H. pylori Infection and Host Autophagy Pathways

Accumulating evidence suggests that H. pylori could invade and multiply in different cell types, such as gastric epithelial cells, macrophage, and dendritic cells [71][76][77]. Terry et al. reported for the first time that attached H. pylori could be engulfed by AGS cells through a zipper-like mechanism involving various cellular signal transduction pathways [78]. Autophagy is considered an innate immune response to restrict intracellular bacteria survival. Generally, host cell autophagy is induced upon bacterial infection, as manifested by the formation of autophagosome around invaded bacteria followed by autophagosome-lysosome fusion to degrade bacteria [79]. Terebiznik et al. found that H. pylori virulence factor VacA induced autophagy in a manner dependent on the channel-forming activity of VacA, but independent of urease, CagA, or type IV secretion system [80]. Low-density lipoprotein receptor-related protein-1 (LRP1) was identified as a receptor for VacA in gastric epithelial cells to induce autophagy [37]. In addition, intracellular pattern recognition receptor NOD1 could interact with the outer membrane vesicles (OMVs) of H. pylori and RIP2 on early endosome to induce cellular autophagy and inflammation, and this effect was independent of VacA [81]. Although autophagy acts as a host innate immune response to eliminate invaded bacteria, H. pylori could exploit autophagy and hijack immature autophagosomes to generate a protected reservoir [80][82]. Although acute exposure to VacA induced autophagy in host cells, prolonged exposure to VacA impaired the autophagic flux mainly due to the deficiency of Cathepsin D (CTSD), a principal lysosomal protease in autophagosomes [83]. Capurro et al. further revealed that VacA inhibited the activity of lysosomal calcium channel TRPML1, resulting in disrupted endolysosomal trafficking and decreased mature cathepsin D levels, thus generating an intracellular niche for H. pylori [84].

3.3. Oxidative and Nitrosative Stress

Colonization of H. pylori in gastric epithelium could induce chronic inflammatory response and recruit phagocytic cells, such as macrophages, neutrophils, and inflammatory monocytes. In phagocytes, NADPH oxidase (NOX) and inducible nitric oxide synthase (iNOS), respectively responsible for the generation of superoxide (O2−) and nitric oxide (NO), are induced to defend against invading pathogens. O2− and its derivatives, known as reactive oxygen species (ROS), as well as NO and its derived intermediates, called reactive nitrogen species (RNS), play important roles in host antimicrobial response [85]. In addition to phagocytic cells, gastric epithelial cells also induce NOX and iNOS upon H. pylori infection, although how these changes contribute to H. pylori-mediated pathogenesis is still controversial [86][87][88].

References

  1. Kusters, G.J.; van Vliet, A.H.; Kuipers, E.J. Pathogenesis of helicobacter pylori infection. Clin. Microbiol. Rev. 2006, 19, 449–490.
  2. Sabbagh, P.; Mohammadnia-Afrouzi, M.; Javanian, M.; Babazadeh, A.; Koppolu, V.; Vasigala, V.R.; Nouri, H.R.; Ebrahimpour, S. Diagnostic methods for helicobacter pylori infection: Ideals, options, and limitations. Eur. J. Clin. Microbiol. Infect. Dis. 2019, 38, 55–66.
  3. Vale, F.F.; Vitor, J.M. Transmission pathway of helicobacter pylori: Does food play a role in rural and urban areas? Int. J. Food Microbiol. 2010, 138, 1–12.
  4. Conteduca, V.; Sansonno, D.; Lauletta, G.; Russi, S.; Ingravallo, G.; Dammacco, F.H. Pylori infection and gastric cancer: State of the art (review). Int. J. Oncol. 2013, 42, 5–18.
  5. Yang, I.; Nell, S.; Suerbaum, S. Survival in hostile territory: The microbiota of the stomach. FEMS Microbiol. Rev. 2013, 37, 736–761.
  6. Oleastro, M.; Menard, A. The role of helicobacter pylori outer membrane proteins in adherence and pathogenesis. Biology 2013, 2, 1110–1134.
  7. Lamb, A.; Chen, L.F. Role of the helicobacter pylori-induced inflammatory response in the development of gastric cancer. J. Cell Biochem. 2013, 114, 491–497.
  8. Huang, Y.; Wang, Q.L.; Cheng, D.D.; Xu, W.T.; Lu, N.H. Adhesion and invasion of gastric mucosa epithelial cells by helicobacter pylori. Front. Cell Infect. Microbiol. 2016, 6, 159.
  9. Ricci, V.; Romano, M.; Boquet, P. Molecular cross-talk between helicobacter pylori and human gastric mucosa. World J. Gastroenterol. 2011, 17, 1383–1399.
  10. Lina, T.T.; Alzahrani, S.; Gonzalez, J.; Pinchuk, I.V.; Beswick, E.J.; Reyes, V.E. Immune evasion strategies used by helicobacter pylori. World J. Gastroenterol. 2014, 20, 12753–12766.
  11. Moretta, A.; Scieuzo, C.; Petrone, A.M.; Salvia, R.; Manniello, M.D.; Franco, A.; Lucchetti, D.; Vassallo, A.; Vogel, H.; Sgambato, A.; et al. Antimicrobial peptides: A new hope in biomedical and pharmaceutical fields. Front. Cell Infect. Microbiol. 2021, 11, 668632.
  12. Grubman, A.; Kaparakis, M.; Viala, J.; Allison, C.; Badea, L.; Karrar, A.; Boneca, I.G.; le Bourhis, L.; Reeve, S.; Smith, I.A.; et al. The innate immune molecule, nod1, regulates direct killing of helicobacter pylori by antimicrobial peptides. Cell Microbiol. 2010, 12, 626–639.
  13. Raju, D.; Hussey, S.; Jones, N.L. Crohn disease atg16l1 polymorphism increases susceptibility to infection with helicobacter pylori in humans. Autophagy 2012, 8, 1387–1388.
  14. Flint, A.; Stintzi, A.; Saraiva, L.M. Oxidative and nitrosative stress defences of helicobacter and campylobacter species that counteract mammalian immunity. FEMS Microbiol. Rev. 2016, 40, 938–960.
  15. Backert, S.; Clyne, M.; Tegtmeyer, N. Molecular mechanisms of gastric epithelial cell adhesion and injection of caga by helicobacter pylori. Cell Commun. Signal 2011, 9, 28.
  16. Matos, R.; Amorim, I.; Magalhaes, A.; Haesebrouck, F.; Gartner, F.; Reis, C.A. Adhesion of helicobacter species to the human gastric mucosa: A deep look into glycans role. Front. Mol. Biosci. 2021, 8, 656439.
  17. Hage, N.; Howard, T.; Phillips, C.; Brassington, C.; Overman, R.; Debreczeni, J.; Gellert, P.; Stolnik, S.; Winkler, G.S.; Falcone, F.H. Structural basis of lewis(b) antigen binding by the helicobacter pylori adhesin baba. Sci. Adv. 2015, 1, e1500315.
  18. Ansari, S.; Yamaoka, Y. Helicobacter pylori baba in adaptation for gastric colonization. World J. Gastroenterol. 2017, 23, 4158–4169.
  19. Kenny, D.T.; Skoog, E.C.; Linden, S.K.; Struwe, W.B.; Rudd, P.M.; Karlsson, N.G. Presence of terminal n-acetylgalactosaminebeta1-4n-acetylglucosamine residues on o-linked oligosaccharides from gastric muc5ac: Involvement in helicobacter pylori colonization? Glycobiology 2012, 22, 1077–1085.
  20. Walz, A.; Odenbreit, S.; Mahdavi, J.; Boren, T.; Ruhl, S. Identification and characterization of binding properties of helicobacter pylori by glycoconjugate arrays. Glycobiology 2005, 15, 700–708.
  21. Ishijima, N.; Suzuki, M.; Ashida, H.; Ichikawa, Y.; Kanegae, Y.; Saito, I.; Boren, T.; Haas, R.; Sasakawa, C.; Mimuro, H. Baba-mediated adherence is a potentiator of the helicobacter pylori type iv secretion system activity. J. Biol. Chem. 2011, 286, 25256–25264.
  22. Ansari, S.; Yamaoka, Y. Helicobacter pylori virulence factor cytotoxin-associated gene a (caga)-mediated gastric pathogenicity. Int. J. Mol. Sci. 2020, 21, 7430.
  23. Cover, T.L.; Lacy, D.B.; Ohi, M.D. The helicobacter pylori cag type iv secretion system. Trends Microbiol. 2020, 28, 682–695.
  24. Schneider, N.; Krishna, U.; Romero-Gallo, J.; Israel, D.A.; Piazuelo, M.B.; Camargo, M.C.; Sicinschi, L.A.; Schneider, B.G.; Correa, P.; Peek, R.M., Jr. Role of helicobacter pylori caga molecular variations in induction of host phenotypes with carcinogenic potential. J. Infect. Dis. 2009, 199, 1218–1221.
  25. Chang, W.L.; Yeh, Y.C.; Sheu, B.S. The impacts of h. Pylori virulence factors on the development of gastroduodenal diseases. J. Biomed. Sci. 2018, 25, 68.
  26. Hatakeyama, M. Structure and function of helicobacter pylori caga, the first-identified bacterial protein involved in human cancer. Proc. Jpn. Acad. Ser. B Phys. Biol. Sci. 2017, 93, 196–219.
  27. Takahashi-Kanemitsu, A.; Knight, C.T.; Hatakeyama, M. Molecular anatomy and pathogenic actions of helicobacter pylori caga that underpin gastric carcinogenesis. Cell Mol. Immunol. 2020, 17, 50–63.
  28. Cover, T.L. Helicobacter pylori diversity and gastric cancer risk. mBio 2016, 7, e01869-15.
  29. Backert, S.; Tegtmeyer, N.; Selbach, M. The versatility of helicobacter pylori caga effector protein functions: The master key hypothesis. Helicobacter 2010, 15, 163–176.
  30. Li, N.; Feng, Y.; Hu, Y.; He, C.; Xie, C.; Ouyang, Y.; Artim, S.C.; Huang, D.; Zhu, Y.; Luo, Z.; et al. Helicobacter pylori caga promotes epithelial mesenchymal transition in gastric carcinogenesis via triggering oncogenic yap pathway. J. Exp. Clin. Cancer Res. 2018, 37, 280.
  31. Xie, C.; Li, N.; Wang, H.; He, C.; Hu, Y.; Peng, C.; Ouyang, Y.; Wang, D.; Xie, Y.; Chen, J.; et al. Inhibition of autophagy aggravates DNA damage response and gastric tumorigenesis via rad51 ubiquitination in response to h. Pylori infection. Gut Microbes 2020, 11, 1567–1589.
  32. Ansari, S.; Yamaoka, Y. Helicobacter pylori virulence factors exploiting gastric colonization and its pathogenicity. Toxins 2019, 11, 677.
  33. Ricci, V. Relationship between vaca toxin and host cell autophagy in helicobacter pylori infection of the human stomach: A few answers, many questions. Toxins 2016, 8, 203.
  34. Seto, K.; Hayashi-Kuwabara, Y.; Yoneta, T.; Suda, H.; Tamaki, H. Vacuolation induced by cytotoxin from helicobacter pylori is mediated by the egf receptor in hela cells. FEBS Lett. 1998, 431, 347–350.
  35. Yahiro, K.; Wada, A.; Nakayama, M.; Kimura, T.; Ogushi, K.; Niidome, T.; Aoyagi, H.; Yoshino, K.; Yonezawa, K.; Moss, J.; et al. Protein-tyrosine phosphatase alpha, rptp alpha, is a helicobacter pylori vaca receptor. J. Biol. Chem. 2003, 278, 19183–19189.
  36. Yahiro, K.; Niidome, T.; Kimura, M.; Hatakeyama, T.; Aoyagi, H.; Kurazono, H.; Imagawa, K.; Wada, A.; Moss, J.; Hirayama, T. Activation of helicobacter pylori vaca toxin by alkaline or acid conditions increases its binding to a 250-kda receptor protein-tyrosine phosphatase beta. J. Biol. Chem. 1999, 274, 36693–36699.
  37. Yahiro, K.; Satoh, M.; Nakano, M.; Hisatsune, J.; Isomoto, H.; Sap, J.; Suzuki, H.; Nomura, F.; Noda, M.; Moss, J.; et al. Low-density lipoprotein receptor-related protein-1 (lrp1) mediates autophagy and apoptosis caused by helicobacter pylori vaca. J. Biol. Chem. 2012, 287, 31104–31115.
  38. Palframan, S.L.; Kwok, T.; Gabriel, K. Vacuolating cytotoxin a (vaca), a key toxin for helicobacter pylori pathogenesis. Front. Cell Infect. Microbiol. 2012, 2, 92.
  39. Yamasaki, E.; Wada, A.; Kumatori, A.; Nakagawa, I.; Funao, J.; Nakayama, M.; Hisatsune, J.; Kimura, M.; Moss, J.; Hirayama, T. Helicobacter pylori vacuolating cytotoxin induces activation of the proapoptotic proteins bax and bak, leading to cytochrome c release and cell death, independent of vacuolation. J. Biol. Chem. 2006, 281, 11250–11259.
  40. Greenfield, L.K.; Jones, N.L. Modulation of autophagy by helicobacter pylori and its role in gastric carcinogenesis. Trends Microbiol. 2013, 21, 602–612.
  41. Trang, T.T.H.; Binh, T.T.; Yamaoka, Y. Relationship between vaca types and development of gastroduodenal diseases. Toxins 2016, 8, 182.
  42. Aftab, H.; Miftahussurur, M.; Subsomwong, P.; Ahmed, F.; Khan, A.K.A.; Matsumoto, T.; Suzuki, R.; Yamaoka, Y. Two populations of less-virulent helicobacter pylori genotypes in bangladesh. PLoS ONE 2017, 12, e0182947.
  43. Sahara, S.; Sugimoto, M.; Vilaichone, R.K.; Mahachai, V.; Miyajima, H.; Furuta, T.; Yamaoka, Y. Role of helicobacter pylori caga epiya motif and vaca genotypes for the development of gastrointestinal diseases in southeast asian countries: A meta-analysis. BMC Infect. Dis. 2012, 12, 223.
  44. Drayton, M.; Deisinger, J.P.; Ludwig, K.C.; Raheem, N.; Muller, A.; Schneider, T.; Straus, S.K. Host defense peptides: Dual antimicrobial and immunomodulatory action. Int. J. Mol. Sci. 2021, 22, 11172.
  45. Huan, Y.; Kong, Q.; Mou, H.; Yi, H. Antimicrobial peptides: Classification, design, application and research progress in multiple fields. Front. Microbiol. 2020, 11, 582779.
  46. Neshani, A.; Zare, H.; Eidgahi, M.R.A.; Chichaklu, A.H.; Movaqar, A.; Ghazvini, K. Review of antimicrobial peptides with anti-helicobacter pylori activity. Helicobacter 2019, 24, e12555.
  47. Wang, G. Human antimicrobial peptides and proteins. Pharmaceuticals 2014, 7, 545–594.
  48. Kosciuczuk, E.M.; Lisowski, P.; Jarczak, J.; Strzalkowska, N.; Jozwik, A.; Horbanczuk, J.; Krzyzewski, J.; Zwierzchowski, L.; Bagnicka, E. Cathelicidins: Family of antimicrobial peptides. A review. Mol. Biol. Rep. 2012, 39, 10957–10970.
  49. Alford, M.A.; Baquir, B.; Santana, F.L.; Haney, E.F.; Hancock, R.E.W. Cathelicidin host defense peptides and inflammatory signaling: Striking a balance. Front. Microbiol. 2020, 11, 1902.
  50. Hase, K.; Murakami, M.; Iimura, M.; Cole, S.P.; Horibe, Y.; Ohtake, T.; Obonyo, M.; Gallo, R.L.; Eckmann, L.; Kagnoff, M.F. Expression of ll-37 by human gastric epithelial cells as a potential host defense mechanism against helicobacter pylori. Gastroenterology 2003, 125, 1613–1625.
  51. Feng, G.J.; Chen, Y.; Li, K. Helicobacter pylori promote inflammation and host defense through the caga-dependent activation of mtorc1. J. Cell Physiol. 2020, 235, 10094–10108.
  52. Zhang, L.; Wu, W.K.; Gallo, R.L.; Fang, E.F.; Hu, W.; Ling, T.K.; Shen, J.; Chan, R.L.; Lu, L.; Luo, X.M.; et al. Critical role of antimicrobial peptide cathelicidin for controlling helicobacter pylori survival and infection. J. Immunol. 2016, 196, 1799–1809.
  53. Zhang, L.; Yu, J.; Wong, C.C.; Ling, T.K.; Li, Z.J.; Chan, K.M.; Ren, S.X.; Shen, J.; Chan, R.L.; Lee, C.C.; et al. Cathelicidin protects against helicobacter pylori colonization and the associated gastritis in mice. Gene Ther. 2013, 20, 751–760.
  54. Bahar, A.A.; Ren, D. Antimicrobial peptides. Pharmaceuticals 2013, 6, 1543–1575.
  55. Dosler, S.; Karaaslan, E. Inhibition and destruction of pseudomonas aeruginosa biofilms by antibiotics and antimicrobial peptides. Peptides 2014, 62, 32–37.
  56. Kumar, P.; Kizhakkedathu, J.N.; Straus, S.K. Antimicrobial peptides: Diversity, mechanism of action and strategies to improve the activity and biocompatibility in vivo. Biomolecules 2018, 8, 4.
  57. Hilchie, A.L.; Wuerth, K.; Hancock, R.E. Immune modulation by multifaceted cationic host defense (antimicrobial) peptides. Nat. Chem. Biol. 2013, 9, 761–768.
  58. Solanki, S.S.; Singh, P.; Kashyap, P.; Sansi, M.S.; Ali, S.A. Promising role of defensins peptides as therapeutics to combat against viral infection. Microb. Pathog. 2021, 155, 104930.
  59. Xu, D.; Lu, W. Defensins: A double-edged sword in host immunity. Front. Immunol. 2020, 11, 764.
  60. Pero, R.; Coretti, L.; Nigro, E.; Lembo, F.; Laneri, S.; Lombardo, B.; Daniele, A.; Scudiero, O. Beta-defensins in the fight against helicobacter pylori. Molecules 2017, 22, 424.
  61. Kocsis, A.K.; Ocsovszky, I.; Tiszlavicz, L.; Tiszlavicz, Z.; Mandi, Y. Helicobacter pylori induces the release of alpha-defensin by human granulocytes. Inflamm. Res. 2009, 58, 241–247.
  62. Isomoto, H.; Mukae, H.; Ishimoto, H.; Date, Y.; Nishi, Y.; Inoue, K.; Wada, A.; Hirayama, T.; Nakazato, M.; Kohno, S. Elevated concentrations of alpha-defensins in gastric juice of patients with helicobacter pylori infection. Am. J. Gastroenterol. 2004, 99, 1916–1923.
  63. O’Neil, D.A.; Cole, S.P.; Martin-Porter, E.; Housley, M.P.; Liu, L.; Ganz, T.; Kagnoff, M.F. Regulation of human beta-defensins by gastric epithelial cells in response to infection with helicobacter pylori or stimulation with interleukin-1. Infect. Immun. 2000, 68, 5412–5415.
  64. Bajaj-Elliott, M.; Fedeli, P.; Smith, G.V.; Domizio, P.; Maher, L.; Ali, R.S.; Quinn, A.G.; Farthing, M.J. Modulation of host antimicrobial peptide (beta-defensins 1 and 2) expression during gastritis. Gut 2002, 51, 356–361.
  65. Semper, R.P.; Vieth, M.; Gerhard, M.; Mejias-Luque, R. Helicobacter pylori exploits the nlrc4 inflammasome to dampen host defenses. J. Immunol. 2019, 203, 2183–2193.
  66. Muhammad, J.S.; Zaidi, S.F.; Zhou, Y.; Sakurai, H.; Sugiyam, T.a. Novel epidermal growth factor receptor pathway mediates release of human beta-defensin 3 from helicobacter pylori-infected gastric epithelial cells. Pathog. Dis. 2016, 74, ftv128.
  67. Otte, J.M.; Neumann, H.M.; Brand, S.; Schrader, H.; Schmidt, W.E.; Schmitz, F. Expression of beta-defensin 4 is increased in human gastritis. Eur. J. Clin. Investig. 2009, 39, 126–138.
  68. Zharkova, M.S.; Orlov, D.S.; Golubeva, O.Y.; Chakchir, O.B.; Eliseev, I.E.; Grinchuk, T.M.; Shamova, O.V. Application of antimicrobial peptides of the innate immune system in combination with conventional antibiotics-a novel way to combat antibiotic resistance? Front. Cell Infect. Microbiol. 2019, 9, 128.
  69. Deretic, V.; Saitoh, T.; Akira, S. Autophagy in infection, inflammation and immunity. Nat. Rev. Immunol. 2013, 13, 722–737.
  70. Dubois, A.; Boren, T. Helicobacter pylori is invasive and it may be a facultative intracellular organism. Cell Microbiol. 2007, 9, 1108–1116.
  71. Bjorkholm, B.; Zhukhovitsky, V.; Lofman, C.; Hulten, K.; Enroth, H.; Block, M.; Rigo, R.; Falk, P.; Engstrand, L. Helicobacter pylori entry into human gastric epithelial cells: A potential determinant of virulence, persistence, and treatment failures. Helicobacter 2000, 5, 148–154.
  72. Deen, N.S.; Huang, S.J.; Gong, L.; Kwok, T.; Devenish, R.J. The impact of autophagic processes on the intracellular fate of helicobacter pylori: More tricks from an enigmatic pathogen? Autophagy 2013, 9, 639–652.
  73. De Duve, C.; Pressman, B.C.; Gianetto, R.; Wattiaux, R.; Appelmans, F. Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue. Biochem. J. 1955, 60, 604–617.
  74. Chang, N.C. Autophagy and stem cells: Self-eating for self-renewal. Front. Cell Dev. Biol. 2020, 8, 138.
  75. Dikic, I.; Elazar, Z. Mechanism and medical implications of mammalian autophagy. Nat. Rev. Mol. Cell Biol. 2018, 19, 349–364.
  76. Wang, Y.H.; Wu, J.J.; Lei, H.Y. When helicobacter pylori invades and replicates in the cells. Autophagy 2009, 5, 540–542.
  77. Ko, G.H.; Kang, S.M.; Kim, Y.K.; Lee, J.H.; Park, C.K.; Youn, H.S.; Baik, S.C.; Cho, M.J.; Lee, W.K.; Rhee, K.H. Invasiveness of helicobacter pylori into human gastric mucosa. Helicobacter 1999, 4, 77–81.
  78. Kwok, T.; Backert, S.; Schwarz, H.; Berger, J.; Meyer, T.F. Specific entry of helicobacter pylori into cultured gastric epithelial cells via a zipper-like mechanism. Infect. Immun. 2002, 70, 2108–2120.
  79. Hu, W.; Chan, H.; Lu, L.; Wong, K.T.; Wong, S.H.; Li, M.X.; Xiao, Z.G.; Cho, C.H.; Gin, T.; Chan, M.T.V.; et al. Autophagy in intracellular bacterial infection. Semin. Cell Dev. Biol. 2020, 101, 41–50.
  80. Terebiznik, M.R.; Raju, D.; Vazquez, C.L.; Torbricki, K.; Kulkarni, R.; Blanke, S.R.; Yoshimori, T.; Colombo, M.I.; Jones, N.L. Effect of helicobacter pylori’s vacuolating cytotoxin on the autophagy pathway in gastric epithelial cells. Autophagy 2009, 5, 370–379.
  81. Irving, A.T.; Mimuro, H.; Kufer, T.A.; Lo, C.; Wheeler, R.; Turner, L.J.; Thomas, B.J.; Malosse, C.; Gantier, M.P.; Casillas, L.N.; et al. The immune receptor nod1 and kinase rip2 interact with bacterial peptidoglycan on early endosomes to promote autophagy and inflammatory signaling. Cell Host Microbe 2014, 15, 623–635.
  82. Orvedahl, A.; Levine, B. Eating the enemy within: Autophagy in infectious diseases. Cell Death Differ. 2009, 16, 57–69.
  83. Raju, D.; Hussey, S.; Ang, M.; Terebiznik, M.R.; Sibony, M.; Galindo-Mata, E.; Gupta, V.; Blanke, S.R.; Delgado, A.; Romero-Gallo, J.; et al. Vacuolating cytotoxin and variants in atg16l1 that disrupt autophagy promote helicobacter pylori infection in humans. Gastroenterology 2012, 142, 1160–1171.
  84. Capurro, M.I.; Greenfield, L.K.; Prashar, A.; Xia, S.; Abdullah, M.; Wong, H.; Zhong, X.Z.; Bertaux-Skeirik, N.; Chakrabarti, J.; Siddiqui, I.; et al. Vaca generates a protective intracellular reservoir for helicobacter pylori that is eliminated by activation of the lysosomal calcium channel trpml1. Nat. Microbiol. 2019, 4, 1411–1423.
  85. Fang, F.C. Antimicrobial reactive oxygen and nitrogen species: Concepts and controversies. Nat. Rev. Microbiol. 2004, 2, 820–832.
  86. Handa, O.; Naito, Y.; Yoshikawa, T. Redox biology and gastric carcinogenesis: The role of helicobacter pylori. Redox Rep. 2011, 16, 1–7.
  87. Angrisano, T.; Lembo, F.; Peluso, S.; Keller, S.; Chiariotti, L.; Pero, R. Helicobacter pylori regulates inos promoter by histone modifications in human gastric epithelial cells. Med. Microbiol. Immunol. 2012, 201, 249–257.
  88. Echizen, K.; Horiuchi, K.; Aoki, Y.; Yamada, Y.; Minamoto, T.; Oshima, H.; Oshima, M. NF-kappab-induced nox1 activation promotes gastric tumorigenesis through the expansion of sox2-positive epithelial cells. Oncogene 2019, 38, 4250–4263.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Microbiology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Judeng Zeng
,
Chuan Xie
,
Lin Zhang
,
Xiaodong Liu
,
Matthew Tak Vai Chan
,
William Ka Kei Wu
,
Huarong Chen
View Times: 416
Entry Collection: Gastrointestinal Disease
Revisions: 2 times (View History)
Update Date: 18 Oct 2022
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback