Table 1.
Evidence supporting the role of KdpD/KdpE in bacterial virulence and survival in cell or animal models.
Figure 1.
Schematic diagram of the varied inputs, accessory proteins, and regulatory effects of KdpD/KdpE.
(A) The conventional model is that KdpD/KdpE stimulates transcription of the Kdp-ATPase in response to cytoplasmic ionic and ATP concentrations and possibly also turgor pressure [9]. (B) In S. aureus KdpD is affected directly or indirectly by QS systems, and KdpE regulates many downstream genes including virulence factors by directly binding to their promoters [17], [18]. (C) In EHEC, KdpE can also be activated by the QseC histidine kinase, which senses host adrenergic signals as well as bacterial quorum sensing (QS) signals [24]. In vitro its regulatory targets include the ler gene, which controls the “locus of enterocyte effacement" (LEE) genes. Under gluconeogenic conditions, KdpE interacts with Cra to optimally regulate ler; both proteins bind to the promoter, perhaps through bending of the DNA [25]. The downstream regulatory cascade is integral to lesion formation in the host gut [24], [25]. (D) Recently identified accessory components in nonpathogenic E. coli link the pathway to additional input stimuli or modulate KdpD activity [34], [37], [50].
Table 2.
Evidence that KdpD/KdpE plays a role in resisting stresses.
Table 3.
Identification of KdpD accessory components in E. coli and M. tuberculosis.
Figure 2.
KdpD/KdpE virulence-related roles across bacterial taxa.
Evidence supporting the role of KdpD/KdpE in virulence (V) or survival (S) is indicated across diverse bacterial species, all of which are capable of intracellular replication to some extent. The relevant references are also indicated. Phylogenetic relationships are as suggested by Battistuzzi et al. (2004) (not drawn to scale) [51].