Authors
Zonglan Yu, Zhenyue Hu, Qianqian Jin, Haoran Zhang, Menglan Chen, Huan Chen, Wei Chen, Juanjuan Gao, Yawen Wang, Yue Wu, Yingli He, Mengzhe Li, Yingqi Xu, James Garnett, Yan Li, Shuai Yuan, Bing Liu
Published in
Nucleic acids research. Volume 54. Issue 14. Jul 17, 2026.
Abstract
Liquid-liquid phase separation (LLPS) organizes biochemical reactions in cells, yet whether this principle contributes to bacteriophage development has remained unclear. During infection, Bacillus phage SPO1 initially relies on host σA-dependent transcription to drive early gene expression before switching to phage-encoded σ factors for middle and late transcription. However, the mechanisms underlying these transitions, particularly how the middle σ factor Gp28 displaces σA, have remained elusive. Here, we show that SPO1 exploits LLPS to orchestrate its transcriptional program. We identify the phage-encoded transcription factor Gp27 as the principal driver of phase separation, forming biomolecular condensates both in vitro and in vivo. Structural and biochemical analyses reveal that Gp27 possesses a modular architecture that promotes condensate formation and concentrates the transcriptional machinery, thereby compensating for the intrinsically weak promoter-binding activity of phage-encoded σ factors. In parallel, we identify SPO1 Gp33 as an inhibitor of σA-dependent transcription whose expression itself depends on LLPS. Gp33 selectively suppresses σA-driven transcription by trapping the RNA polymerase holoenzyme in an inactive state and preventing σA-mediated promoter recognition. Together, these findings uncover LLPS as a previously unrecognized regulatory strategy exploited by bacteriophages, which acting in concert with a phage-encoded transcription inhibitor, as a mechanism governing phage transcriptional progression.
PMID:
42500824
Bibliographic data and abstract were imported from PubMed on 25 Jul 2026.
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