Reversible conjugation of a CBASS nucleotide cyclase regulates bacterial immune response to phage infection (dataset)



16 Bacterial defense systems against bacteriophage infection build the prokaryotic immune17 system and their proper regulation is vital for survival and fitness. While it is important that18 they are readily available in case of infection, in the absence of phage they need to be tightly19 controlled to prevent activation of an unwanted drastic cellular response. Here we describe20 how the bacterial cyclic oligonucleotide-based antiphage signalling system (CBASS) uses its21 intrinsic protein modification system to regulate the activity of the CD-NTase (cGAS/DncV-like22 nucleotidyl-transferase). By integrating a Type II CBASS system from Bacillus cereus into the23 cognate host Bacillus subtilis, we show that the CD-NTase-associated protein 2 (Cap2)24 conjugates the CD-NTase exclusively to the conserved phage shock protein A (PspA) in the25 absence of phage. We further demonstrate that this CD-NTase-PspA conjugation is reversed26 after infection by the endopeptidase Cap3 (CD-NTase-associated protein 3). Finally, we27 propose a model in which the cyclase is inhibited by conjugation to PspA in the absence of28 phage and that this conjugation is released upon infection, priming the CD-NTase for29 activation.
Date made available2024

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