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.
Authors
- Jonathan D. Winkelman (ORCID: https://orcid.org/0000-0002-8870-2917)
- Sampriti Mukherjee (ORCID: https://orcid.org/0000-0002-5509-8776)
- A. K. Mishra (ORCID: https://orcid.org/0009-0008-4817-5850)
- Dimitrios Manias (ORCID: https://orcid.org/0000-0002-7611-3533)
- Gong Chen (ORCID: https://orcid.org/0000-0002-1857-3670)
Institutions
- University of Illinois Chicago (US)
- University of Chicago (US)
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
Funders
- Searle Scholars Program
- National Institutes of Health
- National Institute of General Medical Sciences