Xenogeneic modulation of the ClpCP protease of Bacillus subtilis by a phage-encoded adaptor-like protein

J Biol Chem. 2019 Nov 15;294(46):17501-17511. doi: 10.1074/jbc.RA119.010007. Epub 2019 Jul 30.


Like eukaryotic and archaeal viruses, which coopt the host's cellular pathways for their replication, bacteriophages have evolved strategies to alter the metabolism of their bacterial host. SPO1 bacteriophage infection of Bacillus subtilis results in comprehensive remodeling of cellular processes, leading to conversion of the bacterial cell into a factory for phage progeny production. A cluster of 26 genes in the SPO1 genome, called the host takeover module, encodes for potentially cytotoxic proteins that specifically shut down various processes in the bacterial host, including transcription, DNA synthesis, and cell division. However, the properties and bacterial targets of many genes of the SPO1 host takeover module remain elusive. Through a systematic analysis of gene products encoded by the SPO1 host takeover module, here we identified eight gene products that attenuated B. subtilis growth. Of the eight phage gene products that attenuated bacterial growth, a 25-kDa protein called Gp53 was shown to interact with the AAA+ chaperone protein ClpC of the ClpCP protease of B. subtilis Our results further reveal that Gp53 is a phage-encoded adaptor-like protein that modulates the activity of the ClpCP protease to enable efficient SPO1 phage progeny development. In summary, our findings indicate that the bacterial ClpCP protease is the target of xenogeneic (dys)regulation by a SPO1 phage-derived factor and add Gp53 to the list of antibacterial products that target bacterial protein degradation and therefore may have utility for the development of novel antibacterial agents.

Keywords: ATP-dependent protease; Bacillus; bacteria; bacteriophage; chaperone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacillus Phages / chemistry
  • Bacillus Phages / genetics*
  • Bacillus subtilis / genetics
  • Bacillus subtilis / growth & development
  • Bacillus subtilis / virology*
  • Cell Division / genetics
  • DNA Replication / genetics
  • DNA, Viral / chemistry
  • DNA, Viral / genetics
  • Endopeptidases / chemistry
  • Endopeptidases / genetics
  • Viral Proteins / chemistry
  • Viral Proteins / genetics*


  • DNA, Viral
  • Viral Proteins
  • Endopeptidases