Authors
Huiting, E., Wang, B., Shmidov, E., Musunuri, S., Gitai, Z., Bondy-Denomy, J.
Abstract
CBASS is an immune pathway that recognizes phage infection and generates cyclic nucleotide signals, which directly activate effectors that stop phage replication. Membrane-acting effectors are proposed to induce cell death to prevent phage replication; however, this mechanism has not been assessed with endogenous expression levels of the effector. We therefore sought to determine the cell viability outcomes of the CBASS phospholipase effector (CapV) upon activation with 3',3'-cGAMP signals in Pseudomonas aeruginosa. Here, we surprisingly observe that constitutive 3',3'-cGAMP signaling from the synthase (CdnA) enables robust cell growth and viability while effectively abolishing phage production in a CapV-dependent manner. Exogenous 3',3'-cGAMP also enhances CBASS anti-phage activity and cell growth. Moreover, constitutive activation of the CapV effector induces no cell fitness cost, and blocks replication of many, but not all, phages. This demonstrates that a cyclic nucleotide-activated CBASS effector possess a degree of phage specificity that has been previously overlooked. When CBASS is active, phage transcription and initiation of DNA replication proceed normally, but phages do not reach maximum DNA levels and fewer mature virions are produced. Based on these findings, we propose that CapV interferes with the early stages of phage capsid assembly at the cell membrane and resultantly disrupts DNA packaging. Collectively, we demonstrate that a successful CBASS response antagonizes a late-stage of the phage replication cycle while maintaining cell viability.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 26 Feb 2026.
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