The CgrA and CgrC Proteins Form a Complex That Positively RegulatescupAFimbrial Gene Expression in Pseudomonas aeruginosa
The CgrA and CgrC proteins ofPseudomonas aeruginosaare coregulators that are required for the phase-variable expression of thecupAfimbrial genes. Neither CgrA nor CgrC resembles a classical transcription regulator, and precisely how these proteins exert their regulatory effects oncupAgene expression is poorly understood. Here, we show that CgrA and CgrC interact with one another directly. We identify a mutant of CgrC that is specifically defective for interaction with CgrA and demonstrate that this mutant cannot restore the phase-variable expression of thecupAfimbrial genes to cells of acgrCmutant strain. Using this mutant, we also show that CgrC associates with thecupApromoter regardless of whether or not it interacts with CgrA. Our findings establish that interaction between CgrA and CgrC is required for the phase-variable expression of thecupAfimbrial genes and suggest that CgrC exerts its regulatory effects directly at thecupApromoter, possibly by recruiting CgrA. Because the regions of CgrA and CgrC that we have identified as interacting with one another are highly conserved among orthologs, our findings raise the possibility that CgrA- and CgrC-related regulators present in other bacteria function coordinately through a direct protein-protein interaction.