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It induces vacuolation, disrupts cellular functions, and modulates immune responses, aiding bacterial survival in the harsh gastric environment. Genetic diversity in the vacA gene, particularly alleles like s1 and m1, is associated with more severe clinical outcomes. Recent advances in structural biology, especially cryo-electron microscopy, have revealed VacA\u2019s oligomeric structure and its ability to form anion-selective channels in host cell membranes, providing important insights into its cytotoxic mechanisms. Understanding VacA\u2019s structure and function is essential for unraveling its role in immune evasion and cellular damage. 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Rev. Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/s41571-023-00747-0","article-title":"Global burden of gastric cancer: Epidemiological trends, risk factors, screening and prevention","volume":"20","author":"Thrift","year":"2023","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/s41586-024-07991-z","article-title":"An ancient ecospecies of Helicobacter pylori","volume":"635","author":"Tourrette","year":"2024","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/nrmicro1095","article-title":"Helicobacter pylori VacA, a paradigm for toxin multifunctionality","volume":"3","author":"Cover","year":"2005","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3206","DOI":"10.1002\/ijc.33158","article-title":"VacA genotypes and cagA-EPIYA-C motifs of Helicobacter pylori and gastric histopathological lesions","volume":"147","author":"Benajah","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Thi Huyen Trang, T., Thanh Binh, T., and Yamaoka, Y. (2016). Relationship between vacA Types and Development of Gastroduodenal Diseases. Toxins, 8.","DOI":"10.3390\/toxins8060182"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Oldani, A., Cormont, M., Hofman, V., Chiozzi, V., Oregioni, O., Canonici, A., Sciullo, A., Sommi, P., Fabbri, A., and Ricci, V. (2009). Helicobacter pylori counteracts the apoptotic action of its VacA toxin by injecting the CagA protein into gastric epithelial cells. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000603"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"9661","DOI":"10.1073\/pnas.0502529102","article-title":"Functional antagonism between Helicobacter pylori CagA and vacuolating toxin VacA in control of the NFAT signaling pathway in gastric epithelial cells","volume":"102","author":"Yokoyama","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.chom.2007.09.005","article-title":"Helicobacter pylori dampens gut epithelial self-renewal by inhibiting apoptosis, a bacterial strategy to enhance colonization of the stomach","volume":"2","author":"Mimuro","year":"2007","journal-title":"Cell Host Microbe"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1016\/j.jmb.2019.03.029","article-title":"Cryo-EM Analysis Reveals Structural Basis of Helicobacter pylori VacA Toxin Oligomerization","volume":"431","author":"Su","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6800","DOI":"10.1073\/pnas.1821959116","article-title":"Cryo-EM structures of Helicobacter pylori vacuolating cytotoxin A oligomeric assemblies at near-atomic resolution","volume":"116","author":"Zhang","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"168432","DOI":"10.1016\/j.jmb.2023.168432","article-title":"Structural Analysis of Membrane-associated Forms of Helicobacter pylori VacA Toxin","volume":"436","author":"Connolly","year":"2024","journal-title":"J. Mol. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/mmi.13443","article-title":"Structural organization of membrane-inserted hexamers formed by Helicobacter pylori VacA toxin","volume":"102","author":"Pyburn","year":"2016","journal-title":"Mol. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/j.1574-6968.1999.tb13615.x","article-title":"Regulation of the transcription of genes encoding different virulence factors in Helicobacter pylori by free iron","volume":"175","author":"Szczebara","year":"1999","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1097\/00042737-200012120-00002","article-title":"Iron influences the expression of Helicobacter pylori outer membrane vesicle-associated virulence factors","volume":"12","author":"Keenan","year":"2000","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1111\/mmi.13160","article-title":"Expression of the Helicobacter pylori virulence factor vacuolating cytotoxin A (vacA) is influenced by a potential stem-loop structure in the 5\u2019 untranslated region of the transcript","volume":"98","author":"Amilon","year":"2015","journal-title":"Mol. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"103374","DOI":"10.1016\/j.jprot.2019.05.002","article-title":"Effect of environmental salt concentration on the Helicobacter pylori exoproteome","volume":"202","author":"Caston","year":"2019","journal-title":"J. Proteom."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1128\/IAI.69.1.543-546.2001","article-title":"Carboxy-terminal proteolytic processing of Helicobacter pylori vacuolating toxin","volume":"69","author":"Nguyen","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1111\/j.1365-2958.1994.tb01019.x","article-title":"Genetic analysis of the Helicobacter pylori vacuolating cytotoxin: Structural similarities with the IgA protease type of exported protein","volume":"12","author":"Schmitt","year":"1994","journal-title":"Mol. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.tim.2012.01.008","article-title":"Intoxication strategy of Helicobacter pylori VacA toxin","volume":"20","author":"Boquet","year":"2012","journal-title":"Trends Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"21107","DOI":"10.1074\/jbc.M501042200","article-title":"Functional properties of the p33 and p55 domains of the Helicobacter pylori vacuolating cytotoxin","volume":"280","author":"Torres","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.jmb.2012.11.020","article-title":"Structural analysis of the oligomeric states of Helicobacter pylori VacA toxin","volume":"425","author":"Chambers","year":"2013","journal-title":"J. Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5517","DOI":"10.1093\/emboj\/18.20.5517","article-title":"Formation of anion-selective channels in the cell plasma membrane by the toxin VacA of Helicobacter pylori is required for its biological activity","volume":"18","author":"Brutsche","year":"1999","journal-title":"EMBO J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"19183","DOI":"10.1074\/jbc.M300117200","article-title":"Protein-tyrosine phosphatase alpha, RPTP alpha, is a Helicobacter pylori VacA receptor","volume":"278","author":"Yahiro","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/ng1112","article-title":"Mice deficient in protein tyrosine phosphatase receptor type Z are resistant to gastric ulcer induction by VacA of Helicobacter pylori","volume":"33","author":"Fujikawa","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Gupta, V.R., Patel, H.K., Kostolansky, S.S., Ballivian, R.A., Eichberg, J., and Blanke, S.R. (2008). Sphingomyelin functions as a novel receptor for Helicobacter pylori VacA. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.1000073"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"16293","DOI":"10.1073\/pnas.0707447104","article-title":"Crystal structure of the Helicobacter pylori vacuolating toxin p55 domain","volume":"104","author":"Gangwer","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1073\/pnas.96.5.2001","article-title":"The vacuolating toxin from Helicobacter pylori forms hexameric pores in lipid bilayers at low pH","volume":"96","author":"Czajkowsky","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6361","DOI":"10.1093\/emboj\/19.23.6361","article-title":"The N-terminal 34 kDa fragment of Helicobacter pylori vacuolating cytotoxin targets mitochondria and induces cytochrome c release","volume":"19","author":"Galmiche","year":"2000","journal-title":"EMBO J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5988","DOI":"10.1073\/pnas.0308694101","article-title":"Membrane channel structure of Helicobacter pylori vacuolating toxin: Role of multiple GXXXG motifs in cylindrical channels","volume":"101","author":"Kim","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12101","DOI":"10.1074\/jbc.M212595200","article-title":"Essential role of a GXXXG motif for membrane channel formation by Helicobacter pylori vacuolating toxin","volume":"278","author":"McClain","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/S0014-5793(01)03133-7","article-title":"Vacuolation induced by VacA toxin of Helicobacter pylori requires the intracellular accumulation of membrane permeant bases, Cl\u2212 and water","volume":"508","author":"Morbiato","year":"2001","journal-title":"FEBS Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0014-5793(99)00474-3","article-title":"VacA from Helicobacter pylori: A hexameric chloride channel","volume":"450","author":"Iwamoto","year":"1999","journal-title":"FEBS Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/S0006-3495(99)77301-7","article-title":"Helicobacter pylori vacuolating toxin forms anion-selective channels in planar lipid bilayers: Possible implications for the mechanism of cellular vacuolation","volume":"76","author":"Tombola","year":"1999","journal-title":"Biophys. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1172\/JCI13045","article-title":"The Helicobacter pylori VacA toxin is a urea permease that promotes urea diffusion across epithelia","volume":"108","author":"Tombola","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1042\/BJ20031719","article-title":"Targeting of Helicobacter pylori vacuolating toxin to lipid raft membrane domains analysed by atomic force microscopy","volume":"381","author":"Geisse","year":"2004","journal-title":"Biochem. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"454","DOI":"10.4161\/gmic.27001","article-title":"Signal transduction of Helicobacter pylori during interaction with host cell protein receptors of epithelial and immune cells","volume":"4","author":"Pachathundikandi","year":"2013","journal-title":"Gut Microbes"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1093\/infdis\/166.5.1073","article-title":"Potentiation of Helicobacter pylori vacuolating toxin activity by nicotine and other weak bases","volume":"166","author":"Cover","year":"1992","journal-title":"J. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1006\/mpat.1998.0241","article-title":"Vacuolating cytotoxin purified from Helicobacter pylori causes mitochondrial damage in human gastric cells","volume":"26","author":"Kimura","year":"1999","journal-title":"Microb. Pathog."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5743","DOI":"10.1021\/bi100618g","article-title":"Reconstitution of Helicobacter pylori VacA toxin from purified components","volume":"49","author":"Gangwer","year":"2010","journal-title":"Biochemistry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9307","DOI":"10.1038\/s41598-020-65787-3","article-title":"Chronic in vivo exposure to Helicobacter pylori VacA: Assessing the efficacy of automated and long-term intragastric toxin infusion","volume":"10","author":"Holland","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"31104","DOI":"10.1074\/jbc.M112.387498","article-title":"Low-density lipoprotein receptor-related protein-1 (LRP1) mediates autophagy and apoptosis caused by Helicobacter pylori VacA","volume":"287","author":"Yahiro","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/BF02818613","article-title":"Action site and cellular effects of cytotoxin VacA produced by Helicobacter pylori","volume":"43","author":"Papini","year":"1998","journal-title":"Folia Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1002\/(SICI)1096-9896(199712)183:4<453::AID-PATH950>3.0.CO;2-2","article-title":"Helicobacter pylori vacuolating toxin accumulates within the endosomal-vacuolar compartment of cultured gastric cells and potentiates the vacuolating activity of ammonia","volume":"183","author":"Ricci","year":"1997","journal-title":"J. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"25585","DOI":"10.1074\/jbc.M212445200","article-title":"Involvement of syntaxin 7 in human gastric epithelial cell vacuolation induced by the Helicobacter pylori-produced cytotoxin VacA","volume":"278","author":"Suzuki","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1172\/JCI10254","article-title":"Dynamin is involved in human epithelial cell vacuolation caused by the Helicobacter pylori-produced cytotoxin VacA","volume":"107","author":"Suzuki","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1038\/cdd.2010.42","article-title":"Endosome-mitochondria juxtaposition during apoptosis induced by, H. pylori VacA","volume":"17","author":"Calore","year":"2010","journal-title":"Cell Death Differ."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"122842","DOI":"10.1016\/j.biomaterials.2024.122842","article-title":"Helicobacter pylori VacA-induced mitochondrial damage in the gastric pit cells of the antrum and therapeutic rescue","volume":"314","author":"Son","year":"2025","journal-title":"Biomaterials"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Doma\u0144ska, G., Motz, C., Meinecke, M., Harsman, A., Papatheodorou, P., Reljic, B., Dian-Lothrop, E.A., Galmiche, A., Kepp, O., and Becker, L. (2010). Helicobacter pylori VacA toxin\/subunit p34: Targeting of an anion channel to the inner mitochondrial membrane. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000878"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"16032","DOI":"10.1073\/pnas.1105175108","article-title":"Helicobacter pylori vacuolating cytotoxin A (VacA) engages the mitochondrial fission machinery to induce host cell death","volume":"108","author":"Jain","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"11250","DOI":"10.1074\/jbc.M509404200","article-title":"Helicobacter pylori vacuolating cytotoxin induces activation of the proapoptotic proteins Bax and Bak, leading to cytochrome c release and cell death, independent of vacuolation","volume":"281","author":"Yamasaki","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Akazawa, Y., Isomoto, H., Matsushima, K., Kanda, T., Minami, H., Yamaghchi, N., Taura, N., Shiozawa, K., Ohnita, K., and Takeshima, F. (2013). Endoplasmic reticulum stress contributes to Helicobacter pylori VacA-induced apoptosis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082322"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"15035","DOI":"10.1038\/cddiscovery.2015.35","article-title":"Helicobacter pylori VacA induces apoptosis by accumulation of connexin 43 in autophagic vesicles via a Rac1\/ERK-dependent pathway","volume":"1","author":"Yahiro","year":"2015","journal-title":"Cell Death Discov."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"370","DOI":"10.4161\/auto.5.3.7663","article-title":"Effect of Helicobacter pylori\u2019s vacuolating cytotoxin on the autophagy pathway in gastric epithelial cells","volume":"5","author":"Terebiznik","year":"2009","journal-title":"Autophagy"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1053\/j.gastro.2012.01.043","article-title":"Vacuolating cytotoxin and variants in Atg16L1 that disrupt autophagy promote Helicobacter pylori infection in humans","volume":"142","author":"Raju","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1038\/s41564-019-0441-6","article-title":"VacA generates a protective intracellular reservoir for Helicobacter pylori that is eliminated by activation of the lysosomal calcium channel TRPML1","volume":"4","author":"Capurro","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1080\/15548627.2019.1677322","article-title":"MCOLN1\/TRPML1 inhibition\u2014A novel strategy used by Helicobacter pylori to escape autophagic killing and antibiotic eradication therapy in vivo","volume":"16","author":"Capurro","year":"2020","journal-title":"Autophagy"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Tan, S., Noto, J.M., Romero-Gallo, J., Peek, R.M., and Amieva, M.R. (2011). Helicobacter pylori perturbs iron trafficking in the epithelium to grow on the cell surface. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002050"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.chom.2018.04.006","article-title":"Helicobacter pylori Infection Modulates Host Cell Metabolism through VacA-Dependent Inhibition of mTORC1","volume":"23","author":"Kim","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.chom.2007.11.003","article-title":"Integrin subunit CD18 Is the T-lymphocyte receptor for the Helicobacter pylori vacuolating cytotoxin","volume":"3","author":"Sewald","year":"2008","journal-title":"Cell Host Microbe"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1111\/j.1462-5822.2010.01551.x","article-title":"PKC-dependent endocytosis of the Helicobacter pylori vacuolating cytotoxin in primary T lymphocytes","volume":"13","author":"Sewald","year":"2011","journal-title":"Cell Microbiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1126\/science.1086871","article-title":"Helicobacter pylori vacuolating cytotoxin inhibits T lymphocyte activation","volume":"301","author":"Gebert","year":"2003","journal-title":"Science"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1084\/jem.20030621","article-title":"The Helicobacter pylori vacuolating toxin inhibits T cell activation by two independent mechanisms","volume":"198","author":"Boncristiano","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e00261-19","DOI":"10.1128\/mBio.00261-19","article-title":"Helicobacter pylori VacA Targets Myeloid Cells in the Gastric Lamina Propria To Promote Peripherally Induced Regulatory T-Cell Differentiation and Persistent Infection","volume":"10","author":"Altobelli","year":"2019","journal-title":"mBio"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e00609-12","DOI":"10.1128\/mBio.00609-12","article-title":"Helicobacter pylori VacA suppresses Lactobacillus acidophilus-induced interferon beta signaling in macrophages via alterations in the endocytic pathway","volume":"4","author":"Weiss","year":"2013","journal-title":"mBio"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1084\/jem.187.1.135","article-title":"Selective inhibition of Ii-dependent antigen presentation by Helicobacter pylori toxin VacA","volume":"187","author":"Molinari","year":"1998","journal-title":"J. Exp. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/cmi.2009.26","article-title":"pylori escape host immunoreaction through inhibiting ILK expression by VacA","volume":"6","author":"Yuan","year":"2009","journal-title":"Cell Mol. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4615","DOI":"10.1128\/iai.65.11.4615-4619.1997","article-title":"Detoxification of the Helicobacter pylori cytotoxin","volume":"65","author":"Manetti","year":"1997","journal-title":"Infect. Immun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4476","DOI":"10.1128\/iai.63.11.4476-4480.1995","article-title":"Helicobacter pylori cytotoxin: Importance of native conformation for induction of neutralizing antibodies","volume":"63","author":"Manetti","year":"1995","journal-title":"Infect. Immun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3252","DOI":"10.1128\/IAI.72.6.3252-3259.2004","article-title":"Therapeutic vaccination against Helicobacter pylori in the beagle dog experimental model: Safety, immunogenicity, and efficacy","volume":"72","author":"Rossi","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Guo, L., Hong, D., Wang, S., Zhang, F., Tang, F., Wu, T., Chu, Y., Liu, H., He, M., and Yang, H. (2019). Therapeutic Protection Against H. pylori Infection in Mongolian Gerbils by Oral Immunization with a Tetravalent Epitope-Based Vaccine with Polysaccharide Adjuvant. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01185"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1053\/j.gastro.2008.05.054","article-title":"Safety and immunogenicity of an intramuscular Helicobacter pylori vaccine in noninfected volunteers: A phase I study","volume":"135","author":"Malfertheiner","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"6499","DOI":"10.1128\/JB.183.22.6499-6508.2001","article-title":"A 12-amino-acid segment, present in type s2 but not type s1 Helicobacter pylori VacA proteins, abolishes cytotoxin activity and alters membrane channel formation","volume":"183","author":"McClain","year":"2001","journal-title":"J. Bacteriol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e00032-20","DOI":"10.1128\/IAI.00032-20","article-title":"Functional Properties of Helicobacter pylori VacA Toxin m1 and m2 Variants","volume":"88","author":"Caston","year":"2020","journal-title":"Infect. Immun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e750","DOI":"10.1016\/j.ijid.2013.03.004","article-title":"Genotyping of Helicobacter pylori virulence-associated genes shows high diversity of strains infecting patients in western Venezuela","volume":"17","author":"Chiurillo","year":"2013","journal-title":"Int. J. Infect. Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1053\/j.gastro.2007.06.056","article-title":"A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer","volume":"133","author":"Rhead","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_78","first-page":"E58","article-title":"Associations Between CagA, VacA, and the Clinical Outcomes of Helicobacter pylori Infections in Okinawa, Japan","volume":"63","author":"Inagaki","year":"2017","journal-title":"Kobe J. Med. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1128\/IAI.00052-12","article-title":"The intermediate region of Helicobacter pylori VacA is a determinant of toxin potency in a Jurkat T cell assay","volume":"80","author":"Algood","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1128\/JCM.01782-10","article-title":"Polymorphisms in the intermediate region of VacA impact Helicobacter pylori-induced disease development","volume":"49","author":"Jones","year":"2011","journal-title":"J. Clin. Microbiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1128\/JCM.01815-09","article-title":"Diversity of VacA intermediate region among Helicobacter pylori strains from several regions of the world","volume":"48","author":"Chung","year":"2010","journal-title":"J. Clin. Microbiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3493","DOI":"10.1128\/JCM.00887-09","article-title":"Role of deletion located between the intermediate and middle regions of the Helicobacter pylori VacA gene in cases of gastroduodenal diseases","volume":"47","author":"Ogiwara","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1111\/hel.12284","article-title":"Relevance of Helicobacter pylori vacA 3\u2019-end Region Polymorphism to Gastric Cancer","volume":"21","author":"Bakhti","year":"2016","journal-title":"Helicobacter"},{"key":"ref_84","first-page":"001969","article-title":"Genotypic diversity of the Helicobacter pylori vacA c region and its correlation with gastric disease outcomes","volume":"74","author":"Zahir","year":"2025","journal-title":"J. Med. Microbiol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Xue, Z., Li, W., Ding, H., Pei, F., Zhang, J., Gong, Y., Fan, R., Wang, F., Wang, Y., and Chen, Q. (2024). Virulence gene polymorphisms in Shandong Helicobacter pylori strains and their relevance to gastric cancer. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0309844"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Soyfoo, D.M., Doomah, Y.H., Xu, D., Zhang, C., Sang, H.M., Liu, Y.Y., Zhang, G.X., Jiang, J.X., and Xu, S.F. (2021). New genotypes of Helicobacter pylori VacA d-region identified from global strains. BMC Mol. Cell Biol., 22.","DOI":"10.1186\/s12860-020-00338-2"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"88","DOI":"10.14715\/cmb\/2025.70.1.9","article-title":"Investigating the potential association of Helicobacter pylori cagA, vacA s1\/s2, iceA1, iceA2, babA2, sabA, and oipA genotypes with gastric disease severity","volume":"71","author":"Othman","year":"2025","journal-title":"Cell. Mol. Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.micpath.2017.04.007","article-title":"Helicobacter pylori genotypes determine risk of non-cardia gastric cancer and intestinal- or diffuse-type GC in Ardabil: A very high-risk area in Northwestern Iran","volume":"107","author":"Abdi","year":"2017","journal-title":"Microb. Pathog."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"11409","DOI":"10.1038\/s41598-020-66128-0","article-title":"Helicobacter pylori patient isolates from South Africa and Nigeria differ in virulence factor pathogenicity profile and associated gastric disease outcome","volume":"10","author":"Palamides","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3114","DOI":"10.1128\/JCM.00469-11","article-title":"Characterization of Helicobacter pylori cagA and vacA genotypes among Alaskans and their correlation with clinical disease","volume":"49","author":"Miernyk","year":"2011","journal-title":"J. Clin. Microbiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"5540560","DOI":"10.1155\/2021\/5540560","article-title":"Genotyping of Helicobacter pylori Virulence Genes cagA and vacA: Regional and National Study","volume":"2021","author":"Kishk","year":"2021","journal-title":"Int. J. Microbiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2984","DOI":"10.1128\/JCM.00551-14","article-title":"Vacuolating cytotoxin genotypes are strong markers of gastric cancer and duodenal ulcer-associated Helicobacter pylori strains: A matched case-control study","volume":"52","author":"Memon","year":"2014","journal-title":"J. Clin. Microbiol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Guzm\u00e1n, J., Castillo, D., Gonz\u00e1lez-Siccha, A.D., Bussalleu, A., Trespalacios-Rangel, A.A., Lescano, A.G., and Sauvain, M. (2024). Helicobacter pylori cagA, vacA, iceA and babA Genotypes from Peruvian Patients with Gastric Intestinal Metaplasia. Cancers, 16.","DOI":"10.3390\/cancers16081476"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"22584","DOI":"10.1038\/srep22584","article-title":"Rare Helicobacter pylori Virulence Genotypes in Bhutan","volume":"6","author":"Matsunari","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Idowu, A., Mzukwa, A., Harrison, U., Palamides, P., Haas, R., Mbao, M., Mamdoo, R., Bolon, J., Jolaiya, T., and Smith, S. (2019). Detection of Helicobacter pylori and its virulence genes (CagA, DupA, and VacA) among patients with gastroduodenal diseases in Chris Hani Baragwanath Academic Hospital, South Africa. BMC Gastroenterol., 19.","DOI":"10.1186\/s12876-019-0986-0"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1128\/JCM.37.4.1203-1205.1999","article-title":"Allelic diversity of the Helicobacter pylori vacuolating cytotoxin gene in South Africa: Rarity of the VacA s1a genotype and natural occurrence of an s2\/m1 allele","volume":"37","author":"Letley","year":"1999","journal-title":"J. Clin. Microbiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1136\/gut.45.4.499","article-title":"Heterogeneity in the Helicobacter pylori vacA and cagA genes: Association with gastroduodenal disease in South Africa?","volume":"45","author":"Kidd","year":"1999","journal-title":"Gut"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1007\/s10096-011-1501-x","article-title":"Prevalence and distribution of Helicobacter pylori cagA and vacA genotypes in the Moroccan population with gastric disease","volume":"31","author":"Benajah","year":"2012","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/S0016-5085(99)70065-X","article-title":"Geographic distribution of vacA allelic types of Helicobacter pylori","volume":"116","author":"Figueiredo","year":"1999","journal-title":"Gastroenterology"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"753710","DOI":"10.1155\/2015\/753710","article-title":"Prevalence of Helicobacter pylori vacA, cagA, and iceA Genotypes in Cuban Patients with Upper Gastrointestinal Diseases","volume":"2015","author":"Feliciano","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1590\/S0074-02762010000300016","article-title":"Helicobacter pylori cagA and vacA genotypes in Cuban and Venezuelan populations","volume":"105","author":"Avila","year":"2010","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1111\/j.1523-5378.2007.00534.x","article-title":"Diversity of Helicobacter pylori cagA and vacA genes in Costa Rica: Its relationship with atrophic gastritis and gastric cancer","volume":"12","author":"Con","year":"2007","journal-title":"Helicobacter"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1099\/jmm.0.000660","article-title":"vacA s1m1 genotype and cagA EPIYA-ABC pattern are predominant among Helicobacter pylori strains isolated from Mexican patients with chronic gastritis","volume":"67","year":"2018","journal-title":"J. Med. Microbiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1476-0711-8-14","article-title":"Frequency of vacA, cagA and babA2 virulence markers in Helicobacter pylori strains isolated from Mexican patients with chronic gastritis","volume":"8","author":"Paniagua","year":"2009","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1086\/315864","article-title":"Helicobacter pylori vacA and cagA genotypes in Mexican adults and children","volume":"182","author":"Atherton","year":"2000","journal-title":"J. Infect. Dis."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3001","DOI":"10.1128\/JCM.37.9.3001-3004.1999","article-title":"Colonization of Mexican patients by multiple Helicobacter pylori strains with different vacA and cagA genotypes","volume":"37","author":"Cravioto","year":"1999","journal-title":"J. Clin. Microbiol."},{"key":"ref_107","first-page":"2631","article-title":"Prevalence of cagA, cagM, vacA and oipA genes in isolates of Helicobacter pylori obtained from hospital patients in Northeast Brazil","volume":"55","author":"Bezerra","year":"2024","journal-title":"Braz. J. Microbiol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Bustos-Fraga, S., Salinas-Pinta, M., Vicu\u00f1a-Almeida, Y., de Oliveira, R.B., and Balde\u00f3n-Rojas, L. (2023). Prevalence of Helicobacter pylori genotypes: cagA, vacA (m1), vacA (s1), babA2, dupA, iceA1, oipA and their association with gastrointestinal diseases. A cross-sectional study in Quito-Ecuador. BMC Gastroenterol., 23.","DOI":"10.1186\/s12876-023-02838-9"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Stegmaier, R., Aguila-Torres, P., and Villarroel-Esp\u00edndola, F. (2024). Historical and Molecular Perspectives on the Presence of Helicobacter pylori in Latin America: A Niche to Improve Gastric Cancer Risk Assessment. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031761"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"6366","DOI":"10.3748\/wjg.v11.i40.6366","article-title":"Helicobacter pylori vacA s1a and s1b alleles from clinical isolates from different regions of Chile show a distinct geographic distribution","volume":"11","author":"Diaz","year":"2005","journal-title":"World J. Gastroenterol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1111\/j.1198-743X.2004.00940.x","article-title":"Genetic characterisation of Helicobacter pylori isolates from an Argentinean adult population based on cag pathogenicity island right-end motifs, lspA-glmM polymorphism and iceA and vacA genotypes","volume":"10","author":"Leanza","year":"2004","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Akeel, M., Shehata, A., Elhafey, A., Elmakki, E., Aboshouk, T., Ageely, H., and Mahfouz, M. (2019). Helicobacter pylori vacA, cagA and iceA genotypes in dyspeptic patients from southwestern region, Saudi Arabia: Distribution and association with clinical outcomes and histopathological changes. BMC Gastroenterol., 19.","DOI":"10.1186\/s12876-019-0934-z"},{"key":"ref_113","first-page":"57","article-title":"Diversity of Helicobacter pylori cagA and vacA Genes and Its Relationship with Clinical Outcomes in Azerbaijan, Iran","volume":"3","author":"Ghotaslou","year":"2013","journal-title":"Adv. Pharm. Bull."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.micpath.2017.02.018","article-title":"Prevalence of Helicobacter pylori vacA, cagA, cagE, oipA, iceA, babA2 and babB genotypes in Iranian dyspeptic patients","volume":"105","author":"Dabiri","year":"2017","journal-title":"Microb. Pathog."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1111\/j.1440-1746.2009.05876.x","article-title":"Distribution of Helicobacter pylori cagA, cagE, oipA and vacA in different major ethnic groups in Tehran, Iran","volume":"24","author":"Dabiri","year":"2009","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.actatropica.2005.01.004","article-title":"Distribution of vacA and cagA genotypes of Helicobacter pylori in Kuwait","volume":"93","author":"Mustafa","year":"2005","journal-title":"Acta Trop."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1476-0711-9-10","article-title":"Prevalence of Helicobacter pylori vacA, cagA, iceA and oipA genotypes in Tunisian patients","volume":"9","author":"Fendri","year":"2010","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1097\/MPG.0b013e31818f09f2","article-title":"Prevalence and clinical relevance of cagA, vacA, and iceA genotypes of Helicobacter pylori isolated from Slovenian children","volume":"49","author":"Homan","year":"2009","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1099\/jmm.0.000163","article-title":"Resistance to clarithromycin and genotypes in Helicobacter pylori strains isolated in Sicily","volume":"64","author":"Fasciana","year":"2015","journal-title":"J. Med. Microbiol."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Karlsson, A., Ryberg, A., Dehnoei, M.N., Borch, K., and Monstein, H.J. (2012). Association between cagA and vacA genotypes and pathogenesis in a Helicobacter pylori infected population from South-eastern Sweden. BMC Microbiol., 12.","DOI":"10.1186\/1471-2180-12-129"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1128\/JCM.39.5.1978-1980.2001","article-title":"Evaluation of clarithromycin resistance and cagA and vacA genotyping of Helicobacter pylori strains from the west of Ireland using line probe assays","volume":"39","author":"Ryan","year":"2001","journal-title":"J. Clin. Microbiol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1007\/s10620-014-3319-8","article-title":"Correlation of Helicobacter pylori genotypes with gastric histopathology in the central region of a South-European country","volume":"60","author":"Almeida","year":"2015","journal-title":"Dig. Dis. Sci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1111\/j.1572-0241.1999.01136.x","article-title":"Relation between vacA subtypes, cytotoxin activity, and disease in Helicobacter pylori-infected patients from The Netherlands","volume":"94","author":"Pan","year":"1999","journal-title":"Am. J. Gastroenterol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1128\/JCM.36.4.944-948.1998","article-title":"Diversity of Helicobacter pylori vacA and cagA genes and relationship to VacA and CagA protein expression, cytotoxin production, and associated diseases","volume":"36","author":"Rudi","year":"1998","journal-title":"J. Clin. Microbiol."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Pinto-Ribeiro, I., Ferreira, R.M., Batalha, S., Hlaing, T., Wong, S.I., Carneiro, F., and Figueiredo, C. (2016). Helicobacter pylori vacA Genotypes in Chronic Gastritis and Gastric Carcinoma Patients from Macau, China. Toxins, 8.","DOI":"10.3390\/toxins8050142"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.3892\/etm.2012.704","article-title":"Prevalence of Helicobacter pylori vacA, cagA and iceA genotypes and correlation with clinical outcome","volume":"4","author":"Wei","year":"2012","journal-title":"Exp. Ther. Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.3748\/wjg.v9.i8.1762","article-title":"cagA and vacA genotype of Helicobacter pylori associated with gastric diseases in Xi\u2019an area","volume":"9","author":"Qiao","year":"2003","journal-title":"World J. Gastroenterol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1046\/j.1523-5378.2001.00040.x","article-title":"Distribution of distinct vacA, cagA and iceA alleles in Helicobacter pylori in Hong Kong","volume":"6","author":"Wong","year":"2001","journal-title":"Helicobacter"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1086\/515600","article-title":"Vacuolating toxin production in clinical isolates of Helicobacter pylori with different vacA genotypes","volume":"178","author":"Wang","year":"1998","journal-title":"J. Infect. Dis."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1086\/515601","article-title":"Prevalence of vacuolating cytotoxin production and distribution of distinct vacA alleles in Helicobacter pylori from China","volume":"178","author":"Pan","year":"1998","journal-title":"J. Infect. Dis."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1128\/JCM.05562-11","article-title":"Association between Helicobacter pylori virulence factors and gastroduodenal diseases in Okinawa, Japan","volume":"50","author":"Matsunari","year":"2012","journal-title":"J. Clin. Microbiol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"3906","DOI":"10.1128\/JCM.43.8.3906-3916.2005","article-title":"Distinct diversity of vacA, cagA, and cagE genes of Helicobacter pylori associated with peptic ulcer in Japan","volume":"43","author":"Yamazaki","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1365-2036.2004.01980.x","article-title":"Diversity of vacA and cagA genes of Helicobacter pylori in Japanese children","volume":"20","author":"Azuma","year":"2004","journal-title":"Aliment Pharmacol. Ther."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1128\/JCM.01501-09","article-title":"Epidemiological link between gastric disease and polymorphisms in VacA and CagA","volume":"48","author":"Jang","year":"2010","journal-title":"J. Clin. Microbiol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"351","DOI":"10.3349\/ymj.2002.43.3.351","article-title":"Diverse vacA allelic types of Helicobacter pylori in Korea and clinical correlation","volume":"43","author":"Choe","year":"2002","journal-title":"Yonsei Med. J."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"579","DOI":"10.3346\/jkms.2001.16.5.579","article-title":"Genotyping CagA, VacA subtype, IceA1, and BabA of Helicobacter pylori isolates from Korean patients, and their association with gastroduodenal diseases","volume":"16","author":"Kim","year":"2001","journal-title":"J. Korean Med. Sci."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1007\/s42770-024-01328-8","article-title":"Helicobacter pylori cagA, vacA, and iceA genotypes and clinical outcomes: A cross-sectional study in central Vietnam","volume":"55","author":"Nguyen","year":"2024","journal-title":"Braz. J. Microbiol."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Sahara, S., Sugimoto, M., Vilaichone, R.K., Mahachai, V., Miyajima, H., Furuta, T., and Yamaoka, Y. (2012). 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., 12.","DOI":"10.1186\/1471-2334-12-223"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"101541","DOI":"10.1016\/j.aohep.2024.101541","article-title":"Helicobacter pylori cagA\/vacAs1-m1 strain is associated with high risk of fibrosis in metabolic-dysfunction-associated steatotic liver disease","volume":"29","author":"Maiorana","year":"2024","journal-title":"Ann. Hepatol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.14309\/ajg.0000000000002968","article-title":"ACG Clinical Guideline: Treatment of Helicobacter pylori Infection","volume":"119","author":"Chey","year":"2024","journal-title":"Am. J. Gastroenterol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"13725","DOI":"10.1080\/07391102.2023.2278080","article-title":"Computational insights into VacA toxin inhibition: Harnessing FDA-approved antibiotics against Helicobacter pylori","volume":"42","author":"Kashyap","year":"2024","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_142","first-page":"54825","article-title":"Screening of putative inhibitors for cytotoxin VacA from Helicobacter pylori","volume":"16","author":"Liu","year":"2026","journal-title":"Sci. Rep."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1186\/s10020-025-01349-5","article-title":"Helicobacter pylori VacA modulates TRAF1-mediated 4-1BB\/NF-kappaB axis to induce host apoptosis and chronic inflammatory damage","volume":"31","author":"Yuan","year":"2025","journal-title":"Mol. Med."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jbiotec.2025.03.018","article-title":"Generation of VacA-targeting guide peptides to increase specific antimicrobial peptide toxicity against Helicobacter pylori","volume":"403","author":"Ortiz","year":"2025","journal-title":"J. Biotechnol."},{"key":"ref_145","first-page":"e12","article-title":"Developing a potent vaccine against Helicobacter pylori: Critical considerations and challenges","volume":"27","author":"Menbari","year":"2024","journal-title":"Expert. Rev. Mol. Med."},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Elbehiry, A., Marzouk, E., and Abalkhail, A. (2025). Unraveling Helicobacter pylori: Insights into Pathogenesis, Immune Evasion, and Progress Toward Effective Vaccination. Vaccines, 13.","DOI":"10.3390\/vaccines13070725"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"e0003125","DOI":"10.1128\/cmr.00031-25","article-title":"Lessons learned from successful implementation of tetanus and diphtheria vaccination programs","volume":"38","author":"Slifka","year":"2025","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Utsch, C., and Haas, R. (2016). VacA\u2019s Induction of VacA-Containing Vacuoles (VCVs) and Their Immunomodulatory Activities on Human T Cells. Toxins, 8.","DOI":"10.3390\/toxins8060190"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"15847","DOI":"10.2147\/IJN.S557242","article-title":"Intramuscular All-Trans Retinoic Acid-Adjuvanted Nanovaccine Elicits Robust Mucosal and Systemic Immunity Against Helicobacter pylori","volume":"20","author":"Xu","year":"2025","journal-title":"Int. J. Nanomed."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1128\/IAI.69.2.730-736.2001","article-title":"Vacuolating cytotoxin of Helicobacter pylori plays a role during colonization in a mouse model of infection","volume":"69","author":"Salama","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.bj.2015.06.002","article-title":"Helicobacter pylori infection: An overview of bacterial virulence factors and pathogenesis","volume":"39","author":"Kao","year":"2016","journal-title":"Biomed. J."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/S2468-1253(18)30125-0","article-title":"Efficacy, immunogenicity, and safety of a parenteral vaccine against Helicobacter pylori in healthy volunteers challenged with a Cag-positive strain: A randomised, placebo-controlled phase 1\/2 study","volume":"3","author":"Malfertheiner","year":"2018","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/nrmicro.2015.3","article-title":"Pore-forming toxins: Ancient, but never really out of fashion","volume":"14","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1016\/j.bbamem.2011.07.036","article-title":"Membrane assembly of the cholesterol-dependent cytolysin pore complex","volume":"1818","author":"Hotze","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"6199","DOI":"10.1128\/IAI.73.10.6199-6209.2005","article-title":"Cholesterol-dependent cytolysins, a family of versatile pore-forming toxins","volume":"73","author":"Tweten","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"34642","DOI":"10.1074\/jbc.M203466200","article-title":"Association of Helicobacter pylori vacuolating toxin (VacA) with lipid rafts","volume":"277","author":"Schraw","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Djekic, A., and M\u00fcller, A. (2016). The Immunomodulator VacA Promotes Immune Tolerance and Persistent Helicobacter pylori Infection through Its Activities on T-Cells and Antigen-Presenting Cells. Toxins, 8.","DOI":"10.3390\/toxins8060187"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"fuad024","DOI":"10.1093\/femsre\/fuad024","article-title":"Correction to: RTX proteins: A highly diverse family secreted by a common mechanism","volume":"47","author":"Bumba","year":"2023","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Knapp, O., and Benz, R. (2020). Membrane Activity and Channel Formation of the Adenylate Cyclase Toxin (CyaA) of Bordetella pertussis in Lipid Bilayer Membranes. Toxins, 12.","DOI":"10.3390\/toxins12030169"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"5315","DOI":"10.1093\/emboj\/19.20.5315","article-title":"In vivo covalent cross-linking of cellular actin by the Vibrio cholerae RTX toxin","volume":"19","author":"Fullner","year":"2000","journal-title":"EMBO J."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/s41541-023-00715-w","article-title":"Emerging vaccine strategies against the incessant pneumococcal disease","volume":"8","author":"Duke","year":"2023","journal-title":"NPJ Vaccines"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41541-023-00609-x","article-title":"The Streptococcus pyogenes vaccine landscape","volume":"8","author":"Walkinshaw","year":"2023","journal-title":"NPJ Vaccines"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"2622","DOI":"10.1007\/s13346-026-02128-3","article-title":"Exploitation of cholesterol-dependent cytolysins for targeted biosensing and therapeutic systems","volume":"16","author":"Abanum","year":"2026","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nbt.3037","article-title":"Engineered liposomes sequester bacterial exotoxins and protect from severe invasive infections in mice","volume":"33","author":"Henry","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1034\/j.1600-0463.2000.d01-42.x","article-title":"Mucosal and systemic antibody responses after peroral or intranasal immunization: Effects of conjugation to enterotoxin B subunits and\/or of co-administration with free toxin as adjuvant","volume":"108","author":"Rask","year":"2000","journal-title":"APMIS"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/nnano.2013.54","article-title":"A biomimetic nanosponge that absorbs pore-forming toxins","volume":"8","author":"Hu","year":"2013","journal-title":"Nat. Nanotechnol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/7\/1068\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T04:17:43Z","timestamp":1784866663000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/7\/1068"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,22]]},"references-count":166,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["biom16071068"],"URL":"https:\/\/doi.org\/10.3390\/biom16071068","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,22]]}}}