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

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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Publication Details

Journal
Nature Communications
Published
2025-12-06
DOI
https://doi.org/10.1038/s41467-025-66862-x
Primary Topic
Bacterial biofilms and quorum sensing
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Jonathan D. Winkelman, Sampriti Mukherjee, A. K. Mishra, Dimitrios Manias et al.
Nature Communications
Bacterial biofilms and quorum sensing
article

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

Jonathan D. Winkelman, Sampriti Mukherjee, A. K. Mishra, Dimitrios Manias, Gong Chen
article en

Abstract

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.

Nature CommunicationsVol. 17(1)
University of Illinois Chicago (US), University of Chicago (US)
Searle Scholars Program, National Institutes of Health, National Institute of General Medical Sciences
Openalex Percentile: Top 65%
Bacterial biofilms and quorum sensing
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A light-induced microprotein triggers regulated intramembrane proteolysis to promote photo-sensing in a pathogenic bacterium — Jonathan D. Winkelman, Sampriti Mukherjee, et al. · Nature Communications (2025) | TGRS Research Map | TGRS