Reversible conjugation of a CBASS nucleotide cyclase regulates bacterial immune response to phage infection
Abstract
Prokaryotic antiviral defence systems are frequently toxic for host cells and stringent regulation is required to ensure survival and fitness. These systems must be readily available in case of infection but tightly controlled to prevent activation of an unnecessary cellular response. Here we investigate how the bacterial cyclic oligonucleotide-based antiphage signalling system (CBASS) uses its intrinsic protein modification system to regulate the nucleotide cyclase. By integrating a type II CBASS system from Bacillus cereus into the model organism Bacillus subtilis, we show that the protein-conjugating Cap2 (CBASS associated protein 2) enzyme links the cyclase exclusively to the conserved phage shock protein A (PspA) in the absence of phage. The cyclase–PspA conjugation is reversed by the deconjugating isopeptidase Cap3 (CBASS associated protein 3). We propose a model in which the cyclase is held in an inactive state by conjugation to PspA in the absence of phage, with conjugation released upon infection, priming the cyclase for activation.
Citation
Kruger , L , Gaskell-Mew , L , Graham , S , Shirran , S L , Hertel , R & White , M 2024 , ' Reversible conjugation of a CBASS nucleotide cyclase regulates bacterial immune response to phage infection ' , Nature Microbiology . https://doi.org/10.1038/s41564-024-01670-5
Publication
Nature Microbiology
Status
Peer reviewed
ISSN
2058-5276Type
Journal article
Description
Funding: This work was funded by a European Research Council Advanced Grant (grant number 101018608) to M.F.W. L.K. was funded by an EMBO postdoctoral fellowship (grant number ALTF 234-2022). L.G.-M. was funded by the UKRI Biotechnology and Biological Sciences Research Council (BBSRC) (grant number BB/T00875X/1).Collections
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