Unraveling the Central Role of Global Regulator PprI in Deinococcus radiodurans Through Label-Free Quantitative Proteomics

Background: Deinococcus radiodurans, renowned for its exceptional resistance to radiation, provides a robust model for elucidating cellular stress responses and DNA repair mechanisms. Previous studies have established PprI as a key regulator contributing to radiation resistance through its involvement in DNA damage repair pathways, oxidative stress response, and metabolic regulation. Methods: Building upon these foundations, our study employs label-free quantitative (LFQ) proteomics coupled with high-resolution mass spectrometry to systematically map pprI deletion protein networks by comparing the global proteomic profiles of pprI knockout and wild-type D. radiodurans strains. Results: Under stringent screening criteria, we identified 719 significantly higher and 281 significantly lower abundant proteins in the knockout strain compared to wild-type strains. Functional analysis revealed that PprI deficiency disrupts homologous recombination (HR) repair, activates nucleotide excision repair (NER) and base excision repair (BER) as a compensatory mechanism, and impairs Mn/Fe homeostasis and carotenoid biosynthesis, leading to increased oxidative stress. Furthermore, PprI deficiency induces significant metabolic reprogramming, including impaired purine synthesis, compromised cell wall integrity, etc. Conclusions: These proteomic findings delineate the extensive regulatory network influenced by PprI, revealing coordinated perturbations across multiple stress response systems when PprI is absent.