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<p>Bacterial flagella drive motility and play crucial roles in host–pathogen interactions, as flagellin is recognized by the mammalian immune system and flagellotropic bacteriophages. We recently discovered a family of phage-encoded, RNA-guided transcription factors called TldR that regulate flagellin expression, but the importance of this regulation to host fitness was unclear. Here we use a human clinical <i>Enterobacter</i> isolate encoding a Flagellin Remodeling prophage (FRφ) to show that FRφ exploits TldR and its flagellin isoform to alter the flagellar composition and phenotypic properties of its host. This transformation enhances bacterial motility and mammalian immune evasion, and cryo-EM structures reveal distinct flagellin architectures underlying physiological changes. FRφ also improves colonization in the murine gut, illustrating the beneficial effect of prophage-mediated flagellar remodelling in a host-associated environment. Collectively, our results reveal how RNA-guided transcription factors emerged in a parallel evolutionary path to CRISPR-Cas and were co-opted by phages to remodel the flagellar apparatus and enhance host fitness.</p>

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Temperate phages enhance bacterial host fitness via RNA-guided flagellar remodelling

  • 期刊论文

  • 发表日期：

    2026年5月27日

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  • Matt W. G. Walker,
  • Egill Richard,
  • Tanner Wiegand,
  • Jing Wang,
  • Zaofeng Yang,
  • Americo A. Casas-Ciniglio,
  • Florian T. Hoffmann,
  • Hamna Shahnawaz,
  • Ryan G. Gaudet,
  • Nicholas Arpaia,
  • Israel S. Fernández,
  • Samuel H. Sternberg

摘要

Bacterial flagella drive motility and play crucial roles in host–pathogen interactions, as flagellin is recognized by the mammalian immune system and flagellotropic bacteriophages. We recently discovered a family of phage-encoded, RNA-guided transcription factors called TldR that regulate flagellin expression, but the importance of this regulation to host fitness was unclear. Here we use a human clinical Enterobacter isolate encoding a Flagellin Remodeling prophage (FRφ) to show that FRφ exploits TldR and its flagellin isoform to alter the flagellar composition and phenotypic properties of its host. This transformation enhances bacterial motility and mammalian immune evasion, and cryo-EM structures reveal distinct flagellin architectures underlying physiological changes. FRφ also improves colonization in the murine gut, illustrating the beneficial effect of prophage-mediated flagellar remodelling in a host-associated environment. Collectively, our results reveal how RNA-guided transcription factors emerged in a parallel evolutionary path to CRISPR-Cas and were co-opted by phages to remodel the flagellar apparatus and enhance host fitness.