Article open access publication

The ClpXP protease is dispensable for degradation of unfolded proteins in Staphylococcus aureus

Scientific Reports, Springer Nature, ISSN 2045-2322

Volume 7, 1, 2017

DOI:10.1038/s41598-017-12122-y, Dimensions: pub.1091665834, PMC: PMC5603545, PMID: 28924169,



  1. (1) University of Copenhagen, grid.5254.6, KU
  2. (2) University of Nebraska Medical Center, grid.266813.8
  3. (3) Universidade Nova de Lisboa, grid.10772.33


In living cells intracellular proteolysis is crucial for protein homeostasis, and ClpP proteases are conserved between eubacteria and the organelles of eukaryotic cells. In Staphylococcus aureus, ClpP associates to the substrate specificity factors, ClpX and ClpC forming two ClpP proteases, ClpXP and ClpCP. To address how individual ClpP proteases impact cell physiology, we constructed a S. aureus mutant expressing ClpX with an I265E substitution in the ClpP recognition tripeptide of ClpX. This mutant cannot degrade established ClpXP substrates confirming that the introduced amino acid substitution abolishes ClpXP activity. Phenotypic characterization of this mutant showed that ClpXP activity controls cell size and is required for growth at low temperature. Cells expressing the ClpXI265E variant, in contrast to cells lacking ClpP, are not sensitive to heat-stress and do not accumulate protein aggregates showing that ClpXP is dispensable for degradation of unfolded proteins in S. aureus. Consistent with this finding, transcriptomic profiling revealed strong induction of genes responding to protein folding stress in cells devoid of ClpP, but not in cells lacking only ClpXP. In the latter cells, highly upregulated loci include the urease operon, the pyrimidine biosynthesis operon, the betA-betB operon, and the pathogenicity island, SaPI5, while virulence genes were dramatically down-regulated.


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