The ClpX protease is essential for inactivating the CI master repressor and completing prophage induction in Staphylococcus aureus
Date
18/10/2023Metadata
Show full item recordAbstract
Bacteriophages (phages) are the most abundant biological entities on Earth, exerting a significant influence on the dissemination of bacterial virulence, pathogenicity, and antimicrobial resistance. Temperate phages integrate into the bacterial chromosome in a dormant state through intricate regulatory mechanisms. These mechanisms repress lytic genes while facilitating the expression of integrase and the CI master repressor. Upon bacterial SOS response activation, the CI repressor undergoes auto-cleavage, producing two fragments with the N-terminal domain (NTD) retaining significant DNA-binding ability. The process of relieving CI NTD repression, essential for prophage induction, remains unknown. Here we show a specific interaction between the ClpX protease and CI NTD repressor fragment of phages Ф11 and 80α in Staphylococcus aureus. This interaction is necessary and sufficient for prophage activation after SOS-mediated CI auto-cleavage, defining the final stage in the prophage induction cascade. Our findings unveil unexpected roles of bacterial protease ClpX in phage biology.
Citation
Thabet , M A , Penades , J R & Haag , A 2023 , ' The ClpX protease is essential for inactivating the CI master repressor and completing prophage induction in Staphylococcus aureus ' , Nature Communications , vol. 14 , 6599 . https://doi.org/10.1038/s41467-023-42413-0
Publication
Nature Communications
Status
Peer reviewed
ISSN
2041-1723Type
Journal article
Description
Funding: This work was supported by grants MR/M003876/1 and MR/S00940X/1 from the Medical Research Council (MRC, UK; https://mrc.ukri.org), BB/N002873/1 and BB/S003835/1 from the Biotechnology and Biological Sciences Research Council (BBSRC, UK; https://bbsrc.ukri.org), and Wellcome Trust 201531/Z/16/Z (https://wellcome.org), to J.R.P. M.A.T. was funded by a PhD studentship provided by Al Baha University-Kingdom of Saudi Arabia (bu.edu.sa).Collections
Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.