Transcriptome analysis reveals that the RNA polymerase-binding protein DksA1 has pleiotropic functions in .

The stringent response (SR) is a highly conserved stress response in bacteria. It is composed of two factors, (i) a nucleotide alarmone, guanosine tetra- and pentaphosphate ((p)ppGpp), and (ii) an RNA polymerase-binding protein, DksA, that regulates various phenotypes, including bacterial virulence. The clinically significant opportunistic bacterial pathogen possesses two genes, and , that encode DksA proteins. It remains elusive, however, which of these two genes plays a more important role in SR regulation. In this work, we compared genome-wide, RNA-Seq-based transcriptome profiles of Δ, Δ, and ΔΔ mutants to globally assess the effects of these gene deletions on transcript levels coupled with phenotypic analyses. The Δ mutant exhibited substantial defects in a wide range of phenotypes, including quorum sensing (QS), anaerobiosis, and motility, whereas the Δ mutant exhibited no significant phenotypic changes, suggesting that the gene may not have an essential function in under the conditions used here. Of note, the Δ mutants displayed substantially increased transcription of genes involved in polyamine biosynthesis, and we also detected increased polyamine levels in these mutants. Because SAM is a shared precursor for the production of both QS autoinducers and polyamines, these findings suggest that DksA1 deficiency skews the flow of SAM toward polyamine production rather than to QS signaling. Together, our results indicate that DksA1, but not DksA2, controls many important phenotypes in We conclude that DksA1 may represent a potential target whose inhibition may help manage recalcitrant infections.