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 -