Effector-mediated transcriptional rewiring resolves interbacterial conflict through conserved c-di-GMP antagonism

Microbial competition serves as a fundamental driver for the evolution of offensive and defensive mechanisms among microorganisms. While it is well established that bacteria utilize specialized secretion systems to deliver both toxic and non-toxic effector proteins into competing cells, thereby directly killing them or modulating cellular events, it remains largely unclear whether bacteria can hijack effector proteins derived from competitors to resolve interspecies conflicts. Here, we demonstrate that Pseudomonas protegens employs a sophisticated defense strategy, hijacking LtaE, a non-cytotoxic effector delivered via the type IV secretion system (T4SS) of non-flagellated Lysobacter enzymogenes, to resolve interbacterial conflict through transcriptional reprogramming. Translocated LtaE neutralizes an uncharacterized antibacterial toxin in P. protegens. Surprisingly, as a countermeasure, P. protegens hijacks LtaE to rewire its host signaling hierarchy, converting it into a motility activation switch. Mechanistically, LtaE directly binds to FleQ, the σ54-dependent master regulator of flagellar biosynthesis, shielding it from inhibitory c-di-guanosine monophosphate (GMP) binding-a universal second messenger whose elevated concentration typically inhibits bacterial motility and promotes biofilm formation. Remarkably, the LtaE-FleQ complex remains stable under high c-di-GMP conditions, overriding sessility signals to derepress flagellar gene expression and trigger escape motility. Biochemical analyses reveal that LtaE broadly targets FleQ homologs across pseudomonads through competitive inhibition of c-di-GMP binding, linking competitor detection to motility activation. Our findings establish a novel bacterial conflict-resolution paradigm, demonstrating how non-cytotoxic effectors act as molecular switches to dynamically reprogram transcriptional networks and enhance phenotypic plasticity.