Details
| Original language | English |
|---|---|
| Pages (from-to) | 17501-17511 |
| Number of pages | 11 |
| Journal | Journal of Biological Chemistry |
| Volume | 294 |
| Issue number | 46 |
| Early online date | 30 Jul 2019 |
| Publication status | Published - 15 Nov 2019 |
Abstract
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
- Bacillus Phages/chemistry, Bacillus subtilis/genetics, Cell Division/genetics, DNA Replication/genetics, DNA, Viral/chemistry, Endopeptidases/chemistry, Viral Proteins/chemistry
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology
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In: Journal of Biological Chemistry, Vol. 294, No. 46, 15.11.2019, p. 17501-17511.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Xenogeneic modulation of the ClpCP protease of Bacillus subtilis by a phage-encoded adaptor-like protein
AU - Mulvenna, Nancy
AU - Hantke, Ingo
AU - Burchell, Lynn
AU - Nicod, Sophie
AU - Bell, David
AU - Turgay, Kürşad
AU - Wigneshweraraj, Sivaramesh
N1 - Funding information: This work was supported by Wellcome Trust Investigator Award 100958 (to S. W.) and a Medical Research Council Ph.D. studentship (to N. M.). Work in the laboratory of K. T. was supported by the Deutsche Forschungsgemein-schaft (Tu106/6-2 and Tu106/8-1), and work in the laboratory of D. B. was supported by Engineering and Physical Sciences Research Council funding. This work was supported by Wellcome Trust Investigator Award 100958 (to S. W.) and a Medical Research Council Ph.D. studentship (to N. M.). Work in the laboratory of K. T. was supported by the Deutsche Forschungsgemeinschaft (Tu106/6-2 and Tu106/8-1), and work in the laboratory of D. B. was supported by Engineering and Physical Sciences Research Council funding.
PY - 2019/11/15
Y1 - 2019/11/15
N2 - 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.
AB - 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.
KW - Bacillus Phages/chemistry
KW - Bacillus subtilis/genetics
KW - Cell Division/genetics
KW - DNA Replication/genetics
KW - DNA, Viral/chemistry
KW - Endopeptidases/chemistry
KW - Viral Proteins/chemistry
UR - http://www.scopus.com/inward/record.url?scp=85075094331&partnerID=8YFLogxK
U2 - 10.1101/569657
DO - 10.1101/569657
M3 - Article
C2 - 31362989
AN - SCOPUS:85075094331
VL - 294
SP - 17501
EP - 17511
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 46
ER -