Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Membrane-Bound Protease FtsH Protects PhoP from the Proteolysis by Cytoplasmic ClpAP Protease in Salmonella Typhimurium

  • Hyungkeun Song (Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University) ;
  • Eunna Choi (Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University) ;
  • Eun-Jin Lee (Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University)
  • Received : 2023.06.08
  • Accepted : 2023.06.12
  • Published : 2023.09.28
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Abstract

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.

Keywords

Acknowledgement

We thank Dr. Dongwoo Shin for providing Salmonella protease mutant strains. This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning [NRF-2022R1A2B5B02002256, NRF-2022R1A4A1025913, and NRF-2020M3A9H5104235 to E.-J.L.] and a grant from Korea University.

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