BACKGROUND: Helicobacter pylori infection poses a significant health burden worldwide, and its virulence factor CagA plays a pivotal role in its pathogenesis. METHODS: In this study, the interaction between H. pylori-infected AGS cells and silver nanoparticles (AgNPs) was investigated, with a focus on the modulation of CagA-mediated responses, investigated by western blotting. Both, the dose-dependent efficacy against H. pylori (growth curves, CFU assay) and the impact of the nanoparticles on AGS cells (MTT assay) were elucidated. RESULTS: AGS cells infected with H. pylori displayed dramatic morphological changes, characterized by elongation and a migratory phenotype, attributed to CagA activity. Preincubation of H. pylori with AgNPs affected these morphological changes in a concentration-dependent manner, suggesting a correlation between AgNPs concentration and CagA function. CONCLUSION: Our study highlights the nuanced interplay between host-pathogen interactions and the therapeutic potential of AgNPs in combating H. pylori infection and offers valuable insights into the multifaceted dynamics of CagA mediated responses.

Cancer Cluster Salzburg Salzburg Austria

Center for Tumor Biology and Immunology Paris Lodron University of Salzburg Salzburg Austria

Department of Biosciences and Medical Biology Paris Lodron University of Salzburg Salzburg Austria

Department of Physical Chemistry Palacky University Olomouc Olomouc Czechia

Zobrazit více v PubMed

Alipour M. (2021). Molecular mechanism of helicobacter pylori-induced gastric cancer. J. Gastrointest Cancer 52, 23–30. doi: 10.1007/s12029-020-00518-5 PubMed DOI PMC

Amin M., Hameed S., Ali A., Anwar F., Shahid S. A., Shakir I., et al. . (2014). Green Synthesis of Silver Nanoparticles: Structural Features and in Vivo and in Vitro Therapeutic Effects against Helicobacter pylori Induced Gastritis. Bioinorg. Chem. Appl. 2014, 1–11. doi: 10.1155/2014/135824 PubMed DOI PMC

Asgari S., Nikkam N., Saniee P. (2022). Metallic Nanoparticles as promising tools to eradicate H. Pylori: A. Compr. Rev. Recent Advancements Talanta Open 6, 1–8. doi: 10.1016/j.talo.2022.100129 DOI

Axson J. L., Stark D. I., Bondy A. L., Capracotta S. S., Maynard A. D., Philbert M. A., et al. . (2015). Rapid kinetics of size and pH-dependent dissolution and aggregation of silver nanoparticles in simulated gastric fluid. J. Phys. Chem. C. 119, 20632–20641. doi: 10.1021/acs.jpcc.5b03634 PubMed DOI PMC

Bauer M., Nascakova Z., Mihai A. I., Cheng P. F., Levesque M. P., Lampart S., et al. . (2020). ALPK1/TIFA/NF-κB axis links a bacterial carcinogen to R-loop-induced replication stress. Nat. Commun. 11, 1–16. doi: 10.1038/s41467-020-18857-z PubMed DOI PMC

Boyanova L., Hadzhiyski P., Gergova R., Markovska R. (2023). Evolution of helicobacter pylori resistance to antibiotics: A topic of increasing concern. Antibiotics 12, 1–19. doi: 10.3390/antibiotics12020332 PubMed DOI PMC

Brandt S., Kwok T., Hartig R., Kö W., Backert S. (2005). NF-B activation and potentiation of proinflammatory responses by the Helicobacter pylori CagA protein. PNAS 102, 9300–9305. doi: 10.1073/pnas.0409873102 PubMed DOI PMC

De Matteis V. (2017). Exposure to inorganic nanoparticles: Routes of entry, immune response, biodistribution and in vitro/In vivo toxicity evaluation. Toxics 5, 1–21. doi: 10.3390/toxics5040029 PubMed DOI PMC

Ding Y. M., Li Y. Y., Liu J., Wang J., Wan M., Lin M. J., et al. . (2023). The cure rate of 10-day bismuth-containing quadruple therapy for Helicobacter pylori eradication is equivalent to 14-day: a systematic review and meta-analysis. Clin. Exp. Med. 23, 1033–1043. doi: 10.1007/s10238-022-00953-7 PubMed DOI

El Filaly H., Desterke C., Outlioua A., Badre W., Rabhi M., Karkouri M., et al. . (2023). CXCL-8 as a signature of severe Helicobacter pylori infection and a stimulator of stomach region-dependent immune response. Clin. Immunol. 252, 1–14. doi: 10.1016/j.clim.2023.109648 PubMed DOI

Faass L., Stein S. C., Hauke M., Gapp M., Albanese M., Josenhans C. (2021). Contribution of Heptose Metabolites and the cag Pathogenicity Island to the Activation of Monocytes/Macrophages by Helicobacter pylori. Front. Immunol. 12. doi: 10.3389/fimmu.2021.632154 PubMed DOI PMC

Fernando I., Lu D., Zhou Y. (2020). Interactive influence of extracellular polymeric substances (EPS) and electrolytes on the colloidal stability of silver nanoparticles. Environ. Sci. Nano 7, 186–197. doi: 10.1039/C9EN00861F DOI

Grande R., Sisto F., Puca V., Carradori S., Ronci M., Aceto A., et al. . (2020). Antimicrobial and antibiofilm activities of new synthesized silver ultra-nanoClusters (SUNCs) against helicobacter pylori. Front. Microbiol. 11. doi: 10.3389/fmicb.2020.01705 PubMed DOI PMC

Gurunathan S., Jeong J. K., Han J. W., Zhang X. F., Park J. H., Kim J. H. (2015). Multidimensional effects of biologically synthesized silver nanoparticles in Helicobacter pylori, Helicobacter felis, and human lung (L132) and lung carcinoma A549 cells. Nanoscale Res. Lett. 10, 1–17. doi: 10.1186/s11671-015-0747-0 PubMed DOI PMC

Gurunathan S., Qasim M., Park C., Yoo H., Kim J. H., Hong K. (2018). Cytotoxic potential and molecular pathway analysis of silver nanoparticles in human colon cancer cells HCT116. Int. J. Mol. Sci. 19, 1–19. doi: 10.3390/ijms19082269 PubMed DOI PMC

Hamida R. S., Ali M. A., Goda D. A., Khalil M. I., Redhwan A. (2020). Cytotoxic effect of green silver nanoparticles against ampicillin-resistantKlebsiella pneumoniae. RSC Adv. 10, 21136–21146. doi: 10.1039/D0RA03580G PubMed DOI PMC

Hochvaldová L., Večeřová R., Kolář M., Prucek R., Kvítek L., Lapčík L., et al. . (2022). Antibacterial nanomaterials: Upcoming hope to overcome antibiotic resistance crisis. Nanotechnol. Rev. 11, 1115–1142. doi: 10.1515/ntrev-2022-0059 DOI

Jahan I., Matpan Bekler F., Tunç A., Güven K. (2024). The effects of silver nanoparticles (AgNPs) on thermophilic bacteria: antibacterial, morphological, physiological and biochemical investigations. Microorganisms 12, 1–20. doi: 10.3390/microorganisms12020402 PubMed DOI PMC

Jang Y., Zhang X., Zhu R., Li S., Sun S., Li W., et al. . (2022). Viola betonicifolia-mediated biosynthesis of silver nanoparticles for improved biomedical applications. Front. Microbiol. 13. doi: 10.3389/fmicb.2022.891144 PubMed DOI PMC

Khan M. H., Unnikrishnan S., Ramalingam K. (2023). Antipathogenic efficacy of biogenic silver nanoparticles and antibiofilm activities against multi-drug-resistant ESKAPE pathogens. Appl. Biochem. Biotechnol. 196, 2031–2052. doi: 10.1007/s12010-023-04630-7 PubMed DOI

Krisch L. M., Posselt G., Hammerl P., Wesslera S. (2016). CagA phosphorylation in helicobacter pylori-infected B cells is mediated by the nonreceptor tyrosine kinases of the src and Abl families. Infect. Immun. 84, 2671–2680. doi: 10.1128/IAI.00349-16 PubMed DOI PMC

Kuo C. H., Lu C. Y., Yang Y. C., Chin C., Weng B. C., Liu C. J., et al. . (2014). Does long-term Use of silver nanoparticles have persistent inhibitory effect on H. pylori based on Mongolian gerbil’s model? BioMed. Res. Int. 2014, 1–7. doi: 10.1155/2014/461034 PubMed DOI PMC

Lopez-Carrizales M., Velasco K. I., Castillo C., Flores A., Magaña M., Martinez-Castanon G. A., et al. . (2018). In vitro synergism of silver nanoparticles with antibiotics as an alternative treatment in multiresistant uropathogens. Antibiotics 7, 1–13. doi: 10.3390/antibiotics7020050 PubMed DOI PMC

Malfertheiner P., Camargo M. C., El-Omar E., Liou J. M., Peek R., Schulz C., et al. . (2023). Helicobacter pylori infection. Nat. Rev. Dis. Primers 9, 1–24. doi: 10.1038/s41572-023-00431-8 PubMed DOI PMC

Mansouri F., Saffari M., Moniri R., Abbas Moosavi G., Molaghanbari M., Razavizade M. (2022). Investigation of the effect of silver nanoparticles alone and their combination with clarithromycin on H. pylori isolates. Res. Quare. doi: 10.21203/rs.3.rs-1631922/v1 DOI

Mateo E. M., Jiménez M. (2022). Silver nanoparticle-based therapy: can it be useful to combat multi-drug resistant bacteria? Antibiotics 11, 1–13. doi: 10.3390/antibiotics11091205 PubMed DOI PMC

Moese S., Selbach M., Kwok T., Brinkmann V., König W., Meyer T. F., et al. . (2004). Helicobacter pylori induces AGS cell motility and elongation via independent signaling pathways. Infect. Immun. 72, 3646–3649. doi: 10.1128/IAI.72.6.3646-3649.2004 PubMed DOI PMC

Noga M., Milan J., Frydrych A., Jurowski K. (2023). Toxicological aspects, safety assessment, and green toxicology of silver nanoparticles (AgNPs)—Critical review: state of the art. Int. J. Mol. Sci. 24, 1–27. doi: 10.3390/ijms24065133 PubMed DOI PMC

Panáček A., Kvítek L., Prucek R., Kolář M., Večeřová R., Pizúrová N., et al. . (2006). Silver colloid nanoparticles: Synthesis, characterization, and their antibacterial activity. J. Phys. Chem. B. 110, 16248–16253. doi: 10.1021/jp063826h PubMed DOI

Pfannkuch L., Hurwitz R., Trauisen J., Sigulla J., Poeschke M., Matzner L., et al. . (2019). ADP heptose, a novel pathogen-associated molecular pattern identified in Helicobacter pylori. FASEB J. 33, 9087–9099. doi: 10.1096/fj.201802555R PubMed DOI PMC

Polet M., Laloux L., Cambier S., Ziebel J., Gutleb A. C., Schneider Y. J. (2020). Soluble silver ions from silver nanoparticles induce a polarised secretion of interleukin-8 in differentiated Caco-2 cells. Toxicol. Lett. 325, 14–24. doi: 10.1016/j.toxlet.2020.02.004 PubMed DOI

Poppe M., Feller S. M., Römer G., Wessler S. (2007). Phosphorylation of Helicobacter pylori CagA by c-Abl leads to cell motility. Oncogene 26, 3462–3472. doi: 10.1038/sj.onc.1210139 PubMed DOI

Pormohammad A., Mohtavinejad N., Gholizadeh P., Dabiri H., Salimi Chirani A., Hashemi A., et al. . (2019). Global estimate of gastric cancer in Helicobacter pylori–infected population: A systematic review and meta-analysis. J. Cell Physiol. 234, 1208–1218. doi: 10.1002/jcp.27114 PubMed DOI

Reyes V. E. (2023). Helicobacter pylori and its role in gastric cancer. Microorganisms 11, 1–21. doi: 10.3390/microorganisms11051312 PubMed DOI PMC

Rizzato C., Torres J., Obazee O., Camorlinga-Ponce M., Trujillo E., Stein A., et al. . (2020). Variations in cag pathogenicity island genes of Helicobacter pylori from Latin American groups may influence neoplastic progression to gastric cancer. Sci. Rep. 10, 1–9. doi: 10.1038/s41598-020-63463-0 PubMed DOI PMC

Sah D. K., Arjunan A., Lee B., Jung Y. D. (2023). Reactive oxygen species and H. pylori infection: A comprehensive review of their roles in gastric cancer development. Antioxidants 12, 1–27. doi: 10.3390/antiox12091712 PubMed DOI PMC

Sansonetti P. J., Arondel J., Huerre M., Harada A., Matsushima A. K. (1999). Interleukin-8 controls bacterial transepithelial translocation at the cost of epithelial destruction in experimental shigellosis. Infect Immun 67, 1471–1480. doi: 10.1128/IAI.67.3.1471-1480.1999 PubMed DOI PMC

Saravanakumar K., Chelliah R., MubarakAli D., Oh D. H., Kathiresan K., Wang M. H. (2019). Unveiling the potentials of biocompatible silver nanoparticles on human lung carcinoma A549 cells and Helicobacter pylori. Sci. Rep. 9, 1–8. doi: 10.1038/s41598-019-42112-1 PubMed DOI PMC

Sivera M., Kvitek L., Prucek R., Panacek A., Soukupova J. (2012). Study of silver nanoparticles stabilization performed by gelatin. Adv. Sci. Eng. Med. 3, 155–159. doi: 10.1166/asem.2011.1092 DOI

Slavin Y. N., Asnis J., Häfeli U. O., Bach H. (2017). Metal nanoparticles: Understanding the mechanisms behind antibacterial activity. J. Nanobiotechnol. 15, 1–20. doi: 10.1186/s12951-017-0308-z PubMed DOI PMC

Takahashi-Kanemitsu A., Knight C. T., Hatakeyama M. (2020). Molecular anatomy and pathogenic actions of Helicobacter pylori CagA that underpin gastric carcinogenesis. Cell Mol. Immunol. 17, 50–63. doi: 10.1038/s41423-019-0339-5 PubMed DOI PMC

Wahab S., Khan T., Adil M., Khan A. (2021). Mechanistic aspects of plant-based silver nanoparticles against multi-drug resistant bacteria. Heliyon 7, 1–11. doi: 10.1016/j.heliyon.2021.e07448 PubMed DOI PMC

Wang L., Hu C., Shao L. (2017). The antimicrobial activity of nanoparticles: Present situation and prospects for the future. Int. J. Nanomed. 12, 1227–1249. doi: 10.2147/IJN.S121956 PubMed DOI PMC

Yin X., Lai Y., Du Y., Zhang T., Gao J., Li Z. (2023). Metal-based nanoparticles: A prospective strategy for helicobacter pylori treatment. Int. J. Nanomed. 18, 2413–2429. doi: 10.2147/IJN.S405052 PubMed DOI PMC

Zhang J., Wang F., Yalamarty S. S. K., Filipczak N., Jin Y., Li X. (2022). Nano silver-induced toxicity and associated mechanisms. Int. J. Nanomed. 17, 1851–1864. doi: 10.2147/IJN.S355131 PubMed DOI PMC