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Sa3int phages provide highly human-specific virulence factors that promote immune evasion and survival within the host. The reversible excision of these phages which occurs without phage production and bacterial lysis allows the simultaneous expression of phage virulence genes and the\n                      <jats:italic>hlb<\/jats:italic>\n                      gene where they usually integrate. However, the regulatory mechanisms that control phage assembly and the cross-talk with host factors remain poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      We analyzed the regulatory mechanism controlling late gene transcription of Sa3int phage \u03a613. We identified a functional promoter, P\n                      <jats:sub>23,<\/jats:sub>\n                      located upstream of the late phage genes that control DNA processing and packaging, capsid assembly, bacterial lysis and immune evasion.\n                      <jats:italic>SAOUHSC_02200<\/jats:italic>\n                      , the gene located upstream of P\n                      <jats:sub>23<\/jats:sub>\n                      , encodes for a late transcriptional regulator (Ltr). Mutating the P\n                      <jats:sub>23<\/jats:sub>\n                      TATA-box or the\n                      <jats:italic>ltr<\/jats:italic>\n                      gene abolished P\n                      <jats:sub>23<\/jats:sub>\n                      activity and formation of mature intact phage particles, thus confirming the role of Ltr in regulating P\n                      <jats:sub>23<\/jats:sub>\n                      activity. Four direct repeats upstream of the P\n                      <jats:sub>23<\/jats:sub>\n                      transcriptional start site were identified as potential Ltr binding sites. RT-qPCR analysis confirmed that Ltr-dependent P\n                      <jats:sub>23<\/jats:sub>\n                      activation is essential for the expression of late genes and the subsequent \u03a613 propagation. Furthermore, comparative analysis of P\n                      <jats:sub>23<\/jats:sub>\n                      activity and\n                      <jats:italic>ltr<\/jats:italic>\n                      expression in different host strain backgrounds revealed strain-specific differences that appear to depend on the alternative sigma factor SigB and its downstream effector SpoVG.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Ltr controls the expression of late phage genes, thereby regulating phage assembly and lysis. This process is modulated by SpoVG activity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12985-026-03167-5","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T15:13:54Z","timestamp":1777043634000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The phage \u03a613-encoded transcriptional regulator Ltr controls phage assembly in Staphylococcus aureus"],"prefix":"10.1186","volume":"23","author":[{"given":"Ronja","family":"Dobritz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel","family":"B\u00e4cker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carina","family":"Rohmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalya","family":"Korn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vittoria","family":"Bisanzio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christiane","family":"Wolz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"issue":"12","key":"3167_CR1","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1016\/j.tim.2021.04.008","volume":"29","author":"A Hatoum-Aslan","year":"2021","unstructured":"Hatoum-Aslan A. 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