DnaA binding to oriCII regulates transcription from Pseudomonas aeruginosa gidAB-parAB locus linked to the chromosome segregation and streptomycin resistance

Abstract In many bacteria, the DnaA protein, responsible for chromosome replication initiation, also acts as a transcription factor regulating its own gene expression and the expression of other loci. Here, we show that in the opportunistic human pathogen Pseudomonas aeruginosa , DnaA directly regulates the gidAB-parAB operon. DnaA binds to the DnaA boxes preceding the promoter located upstream of the gidA gene within oriCII and deletions in this region impair gidAB-parAB expression and reduce intracellular ParB levels. Additional regulatory elements, including three internal promoters, further contribute to the multilayered regulatory scheme of the gidAB-parAB operon. Since the products of gidA and gidB (glucose-inhibited cell division proteins) are important for cell growth, division, and survival, and those of parA and parB are central to chromosome segregation, regulation of this operon by DnaA suggests a functional link between replication initiation and the regulation of essential cell-cycle-related processes. These findings indicate a regulatory role for the oriCII region and a new function for DnaA in coordinating the gene expression required for proper replication, chromosome segregation, and bacterial growth in P. aeruginosa . Our data are also clinically significant, demonstrating that P. aeruginosa gidB gene disruption results in higher levels of streptomycin resistance.