The Pho regulon: a huge regulatory network in bacteria

Abstract

One of the most important achievements of bacteria is its capability to adapt to the changing conditions of the environment. The competition for nutrients with other microorganisms, especially in the soil, where nutritional conditions are more variable, has led bacteria to evolve a plethora of mechanisms to rapidly fine-tune the requirements of the cell. One of the essential nutrients that are normally found in low concentrations in nature is inorganic phosphate (Pi). Bacteria, as well as other organisms, have developed several systems to cope for the scarcity of this nutrient. To date, the unique mechanism responding to Pi starvation known in detail is the Pho regulon, which is normally controlled by a two component system and constitutes one of the most sensible and efficient regulatory mechanisms in bacteria. Many new members of the Pho regulon have emerged in the last years in several bacteria; however, there are still many unknown questions regarding the activation and function of the whole system. This review describes the most important findings of the last three decades in relation to Pi regulation in bacteria, including: the PHO box, the Pi signaling pathway and the Pi starvation response. The role of the Pho regulon in nutritional regulation cross-talk, secondary metabolite production, and pathogenesis is discussed in detail.

Keywords: PHO box; Pho regulon; pathogenesis; phosphate; regulatory networks; secondary metabolism.

FIGURE 1

Model of PhoB binding to the DNA in Escherichia coli according to the work of Bachhawat et al. (2005). The non-rotational arrangement would provide an inactive state by positioning the effector domains (EDs) in opposite directions, incompatible with tandem DNA binding. In the rotational arrangement, the receiver domains (RDs) would form a twofold symmetric dimer, while the EDs would bind to DNA with tandem symmetry.

FIGURE 2

Regulatory network involving PhoP and other Streptomyces coelicolor global regulators in the control of Pi and N metabolisms and antibiotic production (see text). Green arrows indicate induction. Circle-ended red lines indicate repression. Rhombus-ended orange lines indicate dual activation/repression or unknown regulation. Dashed lines indicate indirect or uncharacterized links. P indicates activation by phosphorylation. SAMe (S-adenosyl-L-methionine), Pi (inorganic phosphate), and N (nitrogen).