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Osmosensing by the bacterial PhoQ/PhoP two-component system

  1. Victor Sourjika,b,1
  1. aMax Planck Institute for Terrestrial Microbiology, 35043 Marburg, Germany;
  2. bLOEWE Center for Synthetic Microbiology (SYNMIKRO), 35043 Marburg, Germany
  1. Edited by Susan Gottesman, National Institutes of Health, Bethesda, MD, and approved November 6, 2017 (received for review October 5, 2017)


Whether residing in or invading the host, enterobacteria have to deal with host-related stress conditions. These stress factors also serve as sensory cues, informing bacteria that they are present inside the host. Here, we report that the PhoQ/PhoP two-component system, which was known to sense several host-related environmental changes, responds to osmotic upshift, another key stimulus associated with the host. This sensing is proposed to rely on a mechanism that detects changes in the physical properties of the membrane. Thus, a single enterobacterial kinase, PhoQ, senses a major part of host-associated stimuli. The PhoQ-mediated osmosensing increases bacterial fitness under hyperosmotic conditions found inside the host, and it is likely to play an important role in the regulation of virulence.


The PhoQ/PhoP two-component system plays an essential role in the response of enterobacteria to the environment of their mammalian hosts. It is known to sense several stimuli that are potentially associated with the host, including extracellular magnesium limitation, low pH, and the presence of cationic antimicrobial peptides. Here, we show that the PhoQ/PhoP two-component systems of Escherichia coli and Salmonella can also perceive an osmotic upshift, another key stimulus to which bacteria become exposed within the host. In contrast to most previously established stimuli of PhoQ, the detection of osmotic upshift does not require its periplasmic sensor domain. Instead, we show that the activity of PhoQ is affected by the length of the transmembrane (TM) helix as well as by membrane lateral pressure. We therefore propose that osmosensing relies on a conformational change within the TM domain of PhoQ induced by a perturbation in cell membrane thickness and lateral pressure under hyperosmotic conditions. Furthermore, the response mediated by the PhoQ/PhoP two-component system was found to improve bacterial growth recovery under hyperosmotic stress, partly through stabilization of the sigma factor RpoS. Our findings directly link the PhoQ/PhoP two-component system to bacterial osmosensing, suggesting that this system can mediate a concerted response to most of the established host-related cues.


  • ?1To whom correspondence may be addressed. Email: jing.yuan{at}synmikro.mpi-marburg.mpg.de or victor.sourjik{at}synmikro.mpi-marburg.mpg.de.
  • Author contributions: J.Y., F.J., T.G., and V.S. designed research; J.Y., F.J., and T.G. performed research; J.Y., F.J., T.G., and V.S. analyzed data; and J.Y. and V.S. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.danielhellerman.com/lookup/suppl/doi:10.1073/pnas.1717272114/-/DCSupplemental.

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