Membrane-Bound Protease FtsH Protects PhoP from the Proteolysis by Cytoplasmic ClpAP Protease in Salmonella Typhimurium

Hyungkeun Song, Eunna Choi, Eun Jin Lee

Research output: Contribution to journalArticlepeer-review


Among the AAA+ proteases in bacteria, FtsH is a membrane-bound ATP-dependent metalloprotease, which is known to degrade many membrane proteins as well as some cytoplasmic proteins. In the intracellular pathogen Salmonella enterica serovar Typhimurium, FtsH is responsible for the proteolysis of several proteins including MgtC virulence factor and MgtA/MgtB Mg2+ transporters, the transcription of which is controlled by the PhoP/PhoQ two-component regulatory system. Given that PhoP response regulator itself is a cytoplasmic protein and also degraded by the cytoplasmic ClpAP protease, it seems unlikely that FtsH affects PhoP protein levels. Here we report an unexpected role of the FtsH protease protecting PhoP proteolysis from cytoplasmic ClpAP protease. In FtsH-depleted condition, PhoP protein levels decrease by ClpAP proteolysis, lowering protein levels of PhoP-controlled genes. This suggests that FtsH is required for normal activation of PhoP transcription factor. FtsH does not degrade PhoP protein but directly binds to PhoP, thus sequestering PhoP from ClpAP-mediated proteolysis. FtsH's protective effect on PhoP can be overcome by providing excess ClpP. Because PhoP is required for Salmonella's survival inside macrophages and mouse virulence, these data implicate that FtsH's sequestration of PhoP from ClpAP-mediated proteolysis is a mechanism ensuring the amount of PhoP protein during Salmonella infection.

Original languageEnglish
Pages (from-to)1130-1140
Number of pages11
JournalJournal of microbiology and biotechnology
Issue number9
Publication statusPublished - 2023 Sept 28

Bibliographical note

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Copyright © 2023 by the authors.


  • ClpAP protease
  • FtsH protease
  • PhoP/PhoQ two-component system

ASJC Scopus subject areas

  • Biotechnology
  • Applied Microbiology and Biotechnology


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