Many Proteobacteria possess the paralogous PTS(Ntr), in addition to the
sugar transport
phosphotransferase system (PTS). In the PTS(Ntr) phosphoryl-groups are transferred from
phosphoenolpyruvate to
protein EIIA(Ntr) via the
phosphotransferases EI(Ntr) and NPr. The PTS(Ntr) has been implicated in regulation of diverse physiological processes. In Escherichia coli, the PTS(Ntr) plays a role in
potassium homeostasis. In particular, EIIA(Ntr) binds to and stimulates activity of a two-component
histidine kinase (KdpD) resulting in increased expression of the genes encoding the high-affinity K(+) transporter KdpFABC. Here, we show that the
phosphate (pho) regulon is likewise modulated by PTS(Ntr). The pho regulon, which comprises more than 30 genes, is activated by the two-component system PhoR/PhoB under conditions of
phosphate starvation. Mutants lacking EIIA(Ntr) are unable to fully activate the pho genes and exhibit a growth delay upon adaptation to
phosphate limitation. In contrast, pho expression is increased above the wild-type level in mutants deficient for EIIA(Ntr) phosphorylation suggesting that non-phosphorylated EIIA(Ntr) modulates pho.
Protein interaction analyses reveal binding of EIIA(Ntr) to
histidine kinase PhoR. This interaction increases the amount of phosphorylated response regulator PhoB. Thus, EIIA(Ntr) is an accessory
protein that modulates the activities of two distinct sensor
kinases, KdpD and PhoR, in E. coli.