The KdpD/KdpE two-component system: integrating K⁺ homeostasis and virulence

PLoS Pathog. 2013 Mar;9(3):e1003201. doi: 10.1371/journal.ppat.1003201. Epub 2013 Mar 28.

Abstract

The two-component system (TCS) KdpD/KdpE, extensively studied for its regulatory role in potassium (K(+)) transport, has more recently been identified as an adaptive regulator involved in the virulence and intracellular survival of pathogenic bacteria, including Staphylococcus aureus, entero-haemorrhagic Escherichia coli, Salmonella typhimurium, Yersinia pestis, Francisella species, Photorhabdus asymbiotica, and mycobacteria. Key homeostasis requirements monitored by KdpD/KdpE and other TCSs such as PhoP/PhoQ are critical to survival in the stressful conditions encountered by pathogens during host interactions. It follows these TCSs may therefore acquire adaptive roles in response to selective pressures associated with adopting a pathogenic lifestyle. Given the central role of K(+) in virulence, we propose that KdpD/KdpE, as a regulator of a high-affinity K(+) pump, has evolved virulence-related regulatory functions. In support of this hypothesis, we review the role of KdpD/KdpE in bacterial infection and summarize evidence that (i) KdpD/KdpE production is correlated with enhanced virulence and survival, (ii) KdpE regulates a range of virulence loci through direct promoter binding, and (iii) KdpD/KdpE regulation responds to virulence-related conditions including phagocytosis, exposure to microbicides, quorum sensing signals, and host hormones. Furthermore, antimicrobial stress, osmotic stress, and oxidative stress are associated with KdpD/KdpE activity, and the system's accessory components (which allow TCS fine-tuning or crosstalk) provide links to stress response pathways. KdpD/KdpE therefore appears to be an important adaptive TCS employed during host infection, promoting bacterial virulence and survival through mechanisms both related to and distinct from its conserved role in K(+) regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Bacteria / pathogenicity*
  • Bacterial Physiological Phenomena
  • Bacterial Proteins / metabolism*
  • Homeostasis / physiology*
  • Host-Pathogen Interactions
  • Potassium Channels / physiology
  • Protein Kinases / metabolism*
  • Trans-Activators / metabolism*
  • Virulence / physiology

Substances

  • Bacterial Proteins
  • Potassium Channels
  • Trans-Activators
  • Protein Kinases
  • kdpD protein, Bacteria