{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T08:05:55Z","timestamp":1771142755574,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":58,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100009624","name":"Yonsei University College of Dentistry","doi-asserted-by":"publisher","award":["6\u20102020\u20100028"],"award-info":[{"award-number":["6\u20102020\u20100028"]}],"id":[{"id":"10.13039\/501100009624","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Helicobacter"],"published-print":{"date-parts":[[2025,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n Introduction<\/jats:title>\n \n The virulence factor CagA is critical in mediating inflammation, and\n \n Helicobacter pylori<\/jats:italic>\n <\/jats:styled-content>\n PMSS1 dynamically modulates\n cagA<\/jats:italic>\n copy number in response to host immune pressure. Co\u2010infection with\n \n Salmonella enterica serotype Typhimurium<\/jats:italic>\n <\/jats:styled-content>\n has been shown to heighten systemic inflammation and reduce\n \n H. pylori<\/jats:italic>\n <\/jats:styled-content>\n colonization while maintaining type IV secretion system functionality. This suggests that the inflammatory environments induced by co\u2010infection may influence\n \n H. pylori<\/jats:italic>\n <\/jats:styled-content>\n virulence mechanisms. This study investigates whether\n \n H. pylori<\/jats:italic>\n <\/jats:styled-content>\n PMSS1 regulates its\n cagA<\/jats:italic>\n copy number during systemic co\u2010infection in a mouse model.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Across three independent mouse experiments,\n \n H. pylori<\/jats:italic>\n <\/jats:styled-content>\n isolated from control and co\u2010infected mice was analyzed for\n cagA<\/jats:italic>\n gene copy number using quantitative real\u2010time polymerase chain reaction. Three isolates with the highest\n cagA<\/jats:italic>\n copy numbers observed to date were further characterized for their virulence phenotypes and subjected to whole\u2010genome sequencing to identify the mutations associated with co\u2010infection.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n \n H. pylori<\/jats:italic>\n <\/jats:styled-content>\n isolates recovered from the stomachs of co\u2010infected mice exhibited significantly higher\n cagA<\/jats:italic>\n copy numbers than those from control mice, with the mean copy number increasing from 2.64 (\u00b11.03) in the control group to 3.22 (\u00b11.63) in the co\u2010infected group. Three\n \n H. pylori<\/jats:italic>\n <\/jats:styled-content>\n isolates with high\n cagA<\/jats:italic>\n copy numbers (6.1, 9.1, and 11.0 copies) were assessed for virulence features. Notably, two of these isolates maintained elevated\n cagA<\/jats:italic>\n phosphorylation and cell elongation, suggesting their potential relevance as a model for\n \n H. pylori<\/jats:italic>\n <\/jats:styled-content>\n infection studies in mice. Whole\u2010genome sequencing further revealed co\u2010infection\u2010associated nonsynonymous mutations, notably in the\n fur<\/jats:italic>\n gene and membrane transport\u2010related genes such as an MFS transporter and a corrinoid ABC transporter substrate\u2010binding protein.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n These findings suggest that co\u2010infection with\n \n S.<\/jats:italic>\n <\/jats:styled-content>\n promotes an increase in the\n cagA<\/jats:italic>\n copy number, thereby enhancing the virulence potential of\n \n H. pylori<\/jats:italic>\n <\/jats:styled-content>\n . The study highlights the complex interplay between\n \n H. pylori<\/jats:italic>\n <\/jats:styled-content>\n and co\u2010infecting pathogens and their combined impact on\n \n H. pylori<\/jats:italic>\n <\/jats:styled-content>\n \u2010mediated disease, and the utility of high\u2010\n cagA<\/jats:italic>\n copy isolates as valuable models for in\u00a0vivo studies addressing pathogenesis.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/hel.70091","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T04:06:07Z","timestamp":1767067567000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Expansion of\n cagA<\/i>\n Copy Number in\n Helicobacter pylori<\/i>\n During Co\u2010Infection in a Mouse Model"],"prefix":"10.1111","volume":"30","author":[{"given":"Kavinda","family":"Tissera","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory Science, Faculty of Allied Health Sciences University of Peradeniya Peradeniya Sri Lanka"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6604-8435","authenticated-orcid":false,"given":"Ashansa","family":"Ramanayake","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, Oral Science Research Center, Department of Applied Life Science, the Graduate School, BK21 FOUR Project Yonsei University College of Dentistry Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myeong\u2010A","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, Oral Science Research Center, Department of Applied Life Science, the Graduate School, BK21 FOUR Project Yonsei University College of Dentistry Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eui\u2010Jeong","family":"Noh","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, Oral Science Research Center, Department of Applied Life Science, the Graduate School, BK21 FOUR Project Yonsei University College of Dentistry Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4197-2722","authenticated-orcid":false,"given":"Sacheera","family":"Angulmaduwa","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, Oral Science Research Center, Department of Applied Life Science, the Graduate School, BK21 FOUR Project Yonsei University College of Dentistry Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dowon","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, Oral Science Research Center, Department of Applied Life Science, the Graduate School, BK21 FOUR Project Yonsei University College of Dentistry Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3191-2670","authenticated-orcid":false,"given":"Yong\u2010Joon","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Molecular Bioscience and Multidimensional Genomics Research Center Kangwon National University Chuncheon Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9385-2653","authenticated-orcid":false,"given":"Jeong\u2010Heon","family":"Cha","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, Oral Science Research Center, Department of Applied Life Science, the Graduate School, BK21 FOUR Project Yonsei University College of Dentistry Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5457.1497"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711183105"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.158"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1131"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201802555R"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0433-3"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006514"},{"key":"e_1_2_10_10_1","first-page":"187","article-title":"The \n Helicobacter pylori\n Type IV Secretion System Encoded by the Cag Pathogenicity Island: Architecture, Function, 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