Positive Regulation of Photo Sensing in a Human Pathogen

Bacteria must continuously integrate environmental cues to adapt in different ecological niches. This dissertation investigates light sensing in Pseudomonas aeruginosa and demonstrates that it is embedded within a complex regulatory network extending beyond the already established BphP-AlgB two-component system. A central finding is the identification of DimA, a 92-amino acid periplasmic microprotein that couples photo sensing to the regulated intramembrane proteolysis (RIP) pathway. DimA activates the site-I protease AlgW via a conserved C-terminal motif, promoting MucA cleavage, release of the sigma factor AlgU, and increased algB transcription. In parallel, AlgB directly upregulates dimA, establishing a positive feedback loop that amplifies light-dependent signaling. DimA is required for repression of virulence factors, including production of Pseudomonas toxins and biofilm formation, and functions as a global activator of the photosensory regulon. Mechanistically, DimA also seems to act as a temporal regulator. Rapid proteolysis by AlgW in vitro and tightly controlled expression dynamics support a model in which DimA functions as a "hourglass" swiftly terminating the photo sensing response once the light signal is removed. In addition, the hybrid kinase-response regulator PA14_48160 is identified as an important downstream effector required for light-mediated repression. Conclusively, these findings establish photo sensing in P. aeruginosa as a complex, multilayered network and highlight microproteins and hybrid kinases as key regulators of bacterial signal transduction.