The Catabolite Repression Control Protein Crc Regulates the Type III Secretion System Through the Adenylate Cyclase CyaB in Pseudomonas aeruginosa

<i>Pseudomonas aeruginosa</i> is a versatile Gram-negative pathogen that causes various infections in humans. The bacterium possesses a type III secretion system (T3SS) to deliver cytotoxic effector proteins into host cells, which plays an important role in bacterial pathogenesis. The T3SS is regulated by the master regulator ExsA, whose expression is controlled by multiple pathways. Here, we demonstrate that the catabolite repression control protein Crc controls T3SS activity by modulating <i>exsA</i> expression. We find that mutation of <i>crc</i> reduces the intracellular cAMP level by 1.76-fold under T3SS-inducing conditions, leading to approximately 2-fold reduction of the <i>exsA</i> expression. Further investigation reveals that Crc affects the mRNA stability of <i>cyaB</i>, which encodes an adenylate cyclase involved in cAMP synthesis. The <i>cyaB</i> 5'-UTR is identified as a key region through which Crc affects its mRNA stability. Our study elucidates a novel regulatory mechanism by which Crc controls the T3SS through modulating <i>cyaB</i> mRNA stability and subsequent cAMP synthesis under T3SS-inducing conditions.