The global regulator Crc plays a multifaceted role in modulation of type III secretion system in Pseudomonas aeruginosa

The opportunistic pathogen Pseudomonas aeruginosa utilizes type III secretion system (T3SS) to translocate effector proteins into eukaryotic host cells that subvert normal host cell functions to the benefit of the pathogen, and results in serious infections. T3SS in P. aeruginosa is controlled by a complex system of regulatory mechanisms and signaling pathways. In this study, we described that Crc, an RNA‐binding protein, exerts a positive impact on T3SS in P. aeruginosa, as evidenced by promoter activity assays of several key T3SS genes, transcriptomics, RT‐PCR, and immunoblotting in crc mutant. We further demonstrated that the regulatory function of Crc on the T3SS was mediated through the T3SS master regulator ExsA and linked to the Cbr/Crc signaling system. Expression profiling of the crc mutant revealed a downregulation of flagship T3SS genes as well as 16 other genes known to regulate T3SS gene expression in P. aeruginosa. On the basis of these data, we proposed that Crc may exert multifaceted control on the T3SS through various pathways, which may serve to fine‐tune this virulence mechanism in response to environmental changes and nutrient sources. By detailed genetic and transcriptomic analysis this study confirmed the critical role of Crc, a RNA‐binding protein, in the regulation of type III secretion system (T3SS) in Pseudomonas aeruginosa. The regulatory function of Crc on the T3SS was mediated through the T3SS master regulator ExsA and linked to the Cbr/Crc signaling system. Crc seemed to modulate T3SS by participating in many known T3SS‐related regulatory mechanisms. This complex and multi‐faceted effect of Crc may serve to fine‐tune the T3SS to accurately sense and respond to environmental signals and nutrient sources, thereby creating a powerful virulence machinery.