{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:09:10Z","timestamp":1790327350195,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,18]]},"group-title":"Evolutionary Biology","reference-count":33,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH","award":["R03DE034511"],"award-info":[{"award-number":["R03DE034511"]}]},{"name":"NIH","award":["R01DE030121"],"award-info":[{"award-number":["R01DE030121"]}]},{"name":"NIH","award":["R21DE034103"],"award-info":[{"award-number":["R21DE034103"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Integrative and conjugative elements (ICEs) are major drivers of horizontal gene transfer and bacterial genome evolution. Although ICE-encoded regulatory circuits have been extensively characterized, the impact of host physiology on the stability of integrated ICEs remains poorly understood. Here, we identify a host-dependent pathway that links specific host translation perturbations to loss of the ICE Tn\n                  <jats:italic>Smu1<\/jats:italic>\n                  in\n                  <jats:italic>Streptococcus mutans<\/jats:italic>\n                  . Analysis of host-gene deletion mutants revealed that disruption of\n                  <jats:italic>fmt<\/jats:italic>\n                  ,\n                  <jats:italic>rnjA<\/jats:italic>\n                  , or\n                  <jats:italic>rnjB<\/jats:italic>\n                  \u2014three translation-associated host genes\u2014reproducibly promoted Tn\n                  <jats:italic>Smu1<\/jats:italic>\n                  loss through a mechanism that bypasses the canonical ICE-encoded metalloprotease ImmA but remains dependent on the native attachment site\n                  <jats:italic>attR<\/jats:italic>\n                  . This phenotype was selective, as mutations affecting other essential cellular functions, including protein folding, tRNA modification, cell division, and fatty acid biosynthesis, failed to destabilize Tn\n                  <jats:italic>Smu1<\/jats:italic>\n                  despite undergoing the same experimental evolution and accumulating adaptive genomic changes. Preventing Tn\n                  <jats:italic>Smu1<\/jats:italic>\n                  loss in these translation-associated mutants markedly reduced bacterial growth, whereas loss of the element improved fitness, indicating that ICE elimination alleviates the cost associated with Tn\n                  <jats:italic>Smu1<\/jats:italic>\n                  retention under these conditions. Finally, we show that the relationship between host translation and Tn\n                  <jats:italic>Smu1<\/jats:italic>\n                  stability extends to a genetically distinct\n                  <jats:italic>S. mutans<\/jats:italic>\n                  clinical isolate, although with strain-dependent penetrance. Together, these findings identify host translational state as an important physiological determinant of Tn\n                  <jats:italic>Smu1<\/jats:italic>\n                  stability and reveal that bacterial hosts can influence the maintenance of integrated mobile genetic elements through mechanisms that extend beyond element-encoded regulatory circuits.\n                <\/jats:p>","DOI":"10.64898\/2026.09.15.751695","type":"posted-content","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T06:30:16Z","timestamp":1789799416000},"source":"Crossref","is-referenced-by-count":0,"title":["Specific host translation perturbations promote Tn\n                  <i>Smu<\/i>\n                  1 loss independently of the canonical ImmA regulator"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0228-6124","authenticated-orcid":false,"given":"Liang","family":"Bao","sequence":"first","affiliation":[{"name":"Department of Oral and Craniofacial Molecular Biology, Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6097-7583","authenticated-orcid":false,"given":"Todd","family":"Kitten","sequence":"additional","affiliation":[{"name":"Department of Oral and Craniofacial Molecular Biology, Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8368-801X","authenticated-orcid":false,"given":"Ping","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Oral and Craniofacial Molecular Biology, Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092501300675000_2026.09.15.751695v2.1","doi-asserted-by":"publisher","DOI":"10.1111\/1751-7915.14408"},{"key":"2026092501300675000_2026.09.15.751695v2.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2024.102556"},{"key":"2026092501300675000_2026.09.15.751695v2.3","doi-asserted-by":"crossref","unstructured":"Burch CL , Romanchuk A , Kelly M , Wu Y , Jones CD . 2023. 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