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.