The Lon protease negatively regulates pyoluteorin biosynthesis through the Gac/Rsm-RsmE cascade and directly degrades the transcriptional activator PltR in Pseudomonas protegens H78

Abstract

Pyoluteorin (Plt) is a broad-spectrum antibiotic with antibacterial and antifungal activities. In Pseudomonas protegens H78, the Plt biosynthetic operon pltLABCDEFG is transcriptionally activated by the LysR-type regulator PltR and is positively regulated by the Gac/Rsm signal transduction cascade (GacS/A-RsmXYZ-RsmE-pltR/pltAB). Additionally, Plt biosynthesis has been shown to be significantly enhanced by mutation of the Lon protease-encoding gene. This study aims to understand the negative regulation pathway and molecular mechanism by which Lon functions in Plt biosynthesis. lon deletion was first found to improve the antimicrobial ability of strain H78 due to its increased Plt production, while partially inhibiting the growth of H78 strain. Lon protease decreases the abundance and stability of the two-component system response regulator GacA and thus participates in the abovementioned Gac/Rsm cascade and negatively regulates Plt biosynthesis. Similarly, Lon protease also decreases the abundance and stability of transcriptional activator PltR. PltR protein can be directly degraded by the Lon protease but not by a mutated form of Lon protease with an amino acid replacement of S₆₇₄ -A. In summary, Lon protease negatively regulates Plt biosynthesis via both the Gac/Rsm-mediated global regulatory pathway and the direct degradation of the transcriptional activator PltR in P. protegens H78.