Pseudomonas aeruginosa is an opportunistic pathogen with a complex regulatory network controlling its physiology and virulence. A key component of this network is PsrA, a TetR-family transcriptional regulator initially identified as an activator of rpoS. PsrA participates in multiple processes, including stress responses, fatty acid metabolism, quorum sensing, and secretion-mediated mechanisms such as the type III secretion system (T3SS). Depending on promoter context and environmental conditions, PsrA functions as both an activator and a repressor, integrating metabolic cues, particularly long-chain fatty acids, to modulate gene expression. In P. aeruginosa, PsrA indirectly influences quorum sensing through acyl-CoA accumulation and directly represses lasR and rhlR, while also activating the exsCEBA operon, required for T3SS expression during acute infection. PsrA further influences rsmZ expression, modulating RsmA activity and affecting pyocyanin production and biofilm-associated traits and has been linked to integrase expression in integrons. Beyond P. aeruginosa, PsrA orthologs and PsrA-like regulators in genera such as Azotobacter, Legionella, Xanthomonas, and Stenotrophomonas display both conserved and divergent regulatory roles, particularly in lipid metabolism and stress adaptation. These findings support PsrA as a context-dependent regulatory integrator in well-characterized T3SS-positive P. aeruginosa lineages, underscoring important gaps in our understanding of its regulation, evolutionary diversification, and potential relevance for future anti-virulence approaches, although direct therapeutic exploitation remains to be validated.
García-Reyes et al. (Wed,) studied this question.