Editors' ChoiceMicrobiology

New connections: The complexity of simple signaling systems

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Sci. Signal.  10 Apr 2018:
Vol. 11, Issue 525, eaat7921
DOI: 10.1126/scisignal.aat7921

Bacterial two-component systems are efficient and versatile but not always simple.

Although two-component systems (TCSs) exist in plants and fungi, they are most prevalent and most studied in bacteria. These signaling systems are primarily used to alter gene expression in response to specific environmental conditions and are often critical for stimulating the induction of virulence genes when the bacteria are present in an appropriate host. TCSs consist of a sensor histidine kinase (HK) that couples to a specific response regulator (RR), usually a transcription factor. When the sensor HK is activated by binding to or dissociating from a ligand, it undergoes autophosphorylation at a conserved histidine residue and then transfers that phosphoryl group to an aspartate residue in the RR. Phosphorylation causes the RR to become active or to interact with other proteins. Most HKs have phosphatase activity in the absence of inducing conditions, which prevents the RR from becoming activated by other stimuli. The FixL-FixJ TCS of the plant root nodule symbiont Bradyrhizobium japonicum stimulates the expression of genes required for nitrogen fixation only under conditions of low oxygen. In this issue of Science Signaling, Wright et al. combined structural analyses, modeling, and functional studies to determine how the dissociation of oxygen stimulates the HK FixL to undergo autophosphorylation and subsequently transfer the phosphoryl group to the RR FixJ.

FixL is sensitive only to oxygen, but other HKs are sensitive to multiple stimuli. In several bacterial species, the HK PhoQ can be activated by acidic pH, antimicrobial peptides, or conditions of low magnesium. In a paper from the Science Signaling Archives, Choi and Groisman found that the Salmonella-specific protein UgtL enhanced the autophosphorylation of PhoQ and was required for maximal activation of the RR PhoP in acidic conditions, such as those inside host cell phagosomes, but was not required for PhoQ to maximally activate PhoP in response to low magnesium or the presence of antimicrobial peptides. The HK and the RR of a TCS may interact with additional proteins, as in the case of UgtL, to fine-tune the system’s responsiveness, but HKs and RRs are typically not highly promiscuous. HKs and RRs usually act as cognate pairs, with the intrinsic phosphatase activity of HKs preventing their cognate RRs from becoming activated by noncognate HKs. However, there are several examples of HKs that can couple to noncognate RRs. Also from our Archives, Guckes et al. found that the Escherichia coli HK PmrB couples not only to its cognate RR PmrA in the presence of iron, but also to QseB, the cognate RR for the HK QseC. Thus, TCSs may appear on the surface to be remarkably simple, but they are versatile and can be subject to complex regulation.

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