Transposon mutagenesis reveals that the microprotein DimA regulates virulence factors in Pseudomonas aeruginosa, highlighting its role in photo-sensing mechanisms.
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.
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