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<p>Light, a ubiquitous environmental stimulus, shapes behavior and physiology across all domains of life. While photoreceptors are widespread in bacterial genomes, their functional roles and signal transduction mechanisms in non-photosynthetic bacteria remain understudied. Light represses biofilms and virulence factors through a bacteriophytochrome photoreceptor BphP and response regulator AlgB in the human pathogen <i>Pseudomonas aeruginosa</i>. Here, we used transposon mutagenesis screening to identify a conserved hypothetical microprotein, DimA, as the master activator of the photo-sensing cascade. Transcriptomics, luciferase reporter assays and physiological assays revealed that deletion of <i>dimA</i> abolishes light-dependent suppression of virulence factors and biofilms. Mechanistically, we demonstrated that DimA activates the site-I protease AlgW, triggering regulated intramembrane proteolysis of the anti-sigma factor MucA, liberating sigma factor AlgU (σ22), which promotes <i>algB</i> expression. We discovered a positive feedback loop where light-activated AlgB upregulates <i>dimA</i> expression, thereby amplifying the photosensory response. This work establishes DimA as a crucial activator of photo sensing and expands our understanding of bacterial adaptation to changing light environments.</p>

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A light-induced microprotein triggers regulated intramembrane proteolysis to promote photo-sensing in a pathogenic bacterium

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月6日

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  • Dimitrios Manias,
  • Ayushi Mishra,
  • Jonathan D. Winkelman,
  • Gong Chen,
  • Sampriti Mukherjee

摘要

Light, a ubiquitous environmental stimulus, shapes behavior and physiology across all domains of life. While photoreceptors are widespread in bacterial genomes, their functional roles and signal transduction mechanisms in non-photosynthetic bacteria remain understudied. Light represses biofilms and virulence factors through a bacteriophytochrome photoreceptor BphP and response regulator AlgB in the human pathogen Pseudomonas aeruginosa. Here, we used transposon mutagenesis screening to identify a conserved hypothetical microprotein, DimA, as the master activator of the photo-sensing cascade. Transcriptomics, luciferase reporter assays and physiological assays revealed that deletion of dimA abolishes light-dependent suppression of virulence factors and biofilms. Mechanistically, we demonstrated that DimA activates the site-I protease AlgW, triggering regulated intramembrane proteolysis of the anti-sigma factor MucA, liberating sigma factor AlgU (σ22), which promotes algB expression. We discovered a positive feedback loop where light-activated AlgB upregulates dimA expression, thereby amplifying the photosensory response. This work establishes DimA as a crucial activator of photo sensing and expands our understanding of bacterial adaptation to changing light environments.