ArticleVirology journal2025
Glucose-induced active lysogeny of prophage ΦSa3XN promotes Staphylococcus aureus virulence.
Article in Virology journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- The phage Φ13-encoded transcriptional regulator Ltr controls phage assembly in Staphylococcus aureus.Virology journal · 2026Article
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11 authors.
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Abstract
backgroundActive lysogeny is a newly characterized mechanism that the dynamic integration and excision of prophages serve as molecular switches to coordinately regulate bacterial gene expression without generating progeny virions. The Sa3int family phages, the most prevalent prophages in Staphylococcus aureus, specifically integrate into the β-toxin-coding gene hlb. While infection conditions favor the loss of Sa3int phages and the emergence of Hlb-producing variants, highlighting their potential for active lysogeny, the environmental cues and underlying mechanisms controlling the peculiar life cycle of Sa3int phages remain largely unexplored.
methodsIn this study, we identified a Sa3int phage, designated ΦSa3XN, from the methicillin-resistant S. aureus strain XN108. The active lysogeny feature of ΦSa3XN was analyzed by combinational PCR, plaque assay, transmission electron microscopy, and DNase protection assay. Additionally, glucose-induced active lysogeny of ΦSa3XN and its impact on S. aureus virulence were evaluated via reporter assay, electrophoretic mobility shift assay, hemolytic assay, and mouse infection models.
resultsΦSa3XN acts as a genuine molecular switch, capable of excision without producing progeny phages. Glucose serves as an environmental cue that triggers ΦSa3XN excision and reinstates hlb expression, wherein the catabolite control protein A (CcpA) directly binds to the promoter region of cI and suppresses the expression of CI repressor, thus switching the phage life cycle. Moreover, glucose-induced active lysogeny of ΦSa3XN significantly enhances bacterial hemolytic activity, exacerbating skin inflammation and subcutaneous abscess formation in hyperglycemic mice.
conclusionThis study illustrates a novel example of active lysogeny for Sa3int phages and elucidates a glucose-responsive CcpA pathway that regulates ΦSa3XN excision to augment S. aureus virulence, advancing our understanding of the sophisticated interactions between S. aureus and phages.
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