{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:59:28Z","timestamp":1790085568408,"version":"4.0.1"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFA1304000"],"award-info":[{"award-number":["2022YFA1304000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32270071"],"award-info":[{"award-number":["32270071"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32400146"],"award-info":[{"award-number":["32400146"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National College Student Innovation and Entrepreneurship Training Program","award":["202610558194"],"award-info":[{"award-number":["202610558194"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSystems"],"published-print":{"date-parts":[[2026,9,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Oral microbial dysbiosis is associated with nasopharyngeal carcinoma (NPC), yet specific microbial drivers within this niche remain poorly characterized. Through multi-cohort profiling of saliva microbiota, we identified\n                      <jats:italic toggle=\"yes\">Streptococcus<\/jats:italic>\n                      as consistently enriched in NPC, whose abundance positively correlates with advanced clinical stages and poor prognosis. Subsequent functional screening across multiple\n                      <jats:italic toggle=\"yes\">Streptococcus<\/jats:italic>\n                      species revealed\n                      <jats:italic toggle=\"yes\">S. anginosus<\/jats:italic>\n                      as the most potent promoter of NPC progression. At the molecular level, we established the interaction between the bacterial surface protein TMPC and host receptor ANXA2 as the primary signaling axis driving\n                      <jats:italic toggle=\"yes\">S. anginosus<\/jats:italic>\n                      -induced tumorigenesis. Structural analysis revealed that specific conserved residues on TMPC confer\n                      <jats:italic toggle=\"yes\">S. anginosus<\/jats:italic>\n                      with superior ANXA2-binding affinity compared with other streptococci, thereby triggering a robust NF-\u03baB\/TNF\u03b1-mediated pro-inflammatory program. Further underscoring its clinical relevance, high host ANXA2 expression significantly correlates with poorer overall survival in NPC patients. Targeted blockade of this interface using a competitive peptide effectively reduced intratumoral\n                      <jats:italic toggle=\"yes\">S. anginosus<\/jats:italic>\n                      persistence and attenuated tumor progression\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . Collectively, our findings identify\n                      <jats:italic toggle=\"yes\">S. anginosus<\/jats:italic>\n                      as a critical functional driver of NPC, with TMPC-ANXA2 acting as the pivotal molecular bridge coupling intratumoral persistence to a pro-tumorigenic inflammatory program. Targeting this specific host-microbe interface offers a promising non-antibiotic, precision therapeutic approach against microbiome-promoted NPC.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Nasopharyngeal carcinoma (NPC) has complex etiological links to microbial dysbiosis. Our study identifies\n                        <jats:italic toggle=\"yes\">S. anginosus<\/jats:italic>\n                        as a key microbial driver, hijacking host ANXA2 via its surface protein TMPC to activate NF-\u03baB\/TNF\u03b1 inflammatory signaling, promoting tumor progression. Structural insights into this interaction reveal targets for therapeutic intervention, with a competitive peptide showing efficacy in reducing bacterial persistence and tumor growth\n                        <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                        . This work redefines\n                        <jats:italic toggle=\"yes\">S. anginosus<\/jats:italic>\n                        as a functional contributor to NPC, offering novel non-antibiotic strategies for targeting microbiota-driven cancers.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msystems.00357-26","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:00:11Z","timestamp":1787662811000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Integrative microbiome and functional profiling identify\n                    <i>Streptococcus anginosus<\/i>\n                    as a pro-tumorigenic driver in nasopharyngeal carcinoma"],"prefix":"10.1128","volume":"11","author":[{"given":"Yifan","family":"Zhu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0064kty71","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Immunology and Microbiology, Zhongshan School of Medicine, Sun Yat-sen University","place":["Guangzhou, China"]},{"id":[{"id":"https:\/\/ror.org\/0064kty71","id-type":"ROR","asserted-by":"publisher"}],"name":"Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewei","family":"Zhou","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0064kty71","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Immunology and Microbiology, Zhongshan School of Medicine, Sun Yat-sen University","place":["Guangzhou, 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