{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T01:01:26Z","timestamp":1781830886727,"version":"3.54.5"},"reference-count":32,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T00:00:00Z","timestamp":1755907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82402038"],"award-info":[{"award-number":["82402038"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515013277"],"award-info":[{"award-number":["2024A1515013277"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ20230807095808017"],"award-info":[{"award-number":["JCYJ20230807095808017"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics"],"published-print":{"date-parts":[[2025,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n Listeria monocytogenes<\/jats:italic>\n represents a significant zoonotic pathogen that completes its infectious cycle by invading intestinal epithelial cells, breaching mucosal barriers, and disseminating to target organs such as the liver and spleen. During this process, the innate immune system, particularly macrophages and dendritic cells, plays a pivotal role in pathogen clearance. In this study, we established an in vitro infection model utilizing Raw264.7 macrophages, DC2.4 dendritic cells, HeLa, and Caco\u20102 epithelial cells. We demonstrated\n L. monocytogenes<\/jats:italic>\n infection significantly upregulates the expression of Ap2s1, a key subunit of the AP\u20102 adaptor complex, in host cells. Subsequent proteomic analysis revealed that two additional AP\u20102 complex subunits, Ap2m1 and Ap2a2, functionally cooperate with Ap2s1 during infection. Genetic knockout experiments confirmed that specific silencing of any of these three subunits, Ap2m1, Ap2a2, or Ap2s1, markedly inhibited intracellular bacterial proliferation. These findings establish the AP\u20102 complex as a promising molecular target for developing novel therapeutic strategies against\n L. monocytogenes<\/jats:italic>\n infections.\n <\/jats:p>\n <\/jats:sec>\n \n Summary<\/jats:title>\n \n \n \n \n This study unveils a critical role of the AP\u20102 adaptor complex in\n L. monocytogenes<\/jats:italic>\n intracellular replication, identifying three subunits, Ap2s1, Ap2m1, and Ap2a2, as key host factors exploited by the pathogen.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Using proteomics and CRISPR\/Cas9\u2010mediated knockout models, we demonstrate that\n L. monocytogenes<\/jats:italic>\n infection upregulates Ap2s1 expression, and depletion of AP\u20102 subunit significantly impairs bacterial proliferation.\n <\/jats:p>\n <\/jats:list-item>\n \n Our findings reveal that AP\u20102 facilitates post\u2010phagosomal cytosolic replication, independent of bacterial cell\u2010to\u2010cell spread.<\/jats:p>\n <\/jats:list-item>\n \n \n This study demonstrates that the AP\u20102 complex may represent a host factor exploited by\n L. monocytogenes<\/jats:italic>\n to promote intracellular replication, offering a novel host\u2010directed therapeutic target to combat antibiotic\u2010resistant strains.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/pmic.70034","type":"journal-article","created":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T12:31:35Z","timestamp":1755952295000},"page":"26-38","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Proteomics Reveals AP\u20102 Complex Depletion Suppressing\n Listeria monocytogenes<\/i>\n Intracellular Replication"],"prefix":"10.1002","volume":"25","author":[{"given":"Zhangfu","family":"Li","sequence":"first","affiliation":[{"name":"Hepato\u2010Pancreato\u2010Biliary Surgery Peking University Shenzhen Hospital Shenzhen Guangdong China"},{"name":"Department of Oral 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