Pycsar (pyrimidine cyclase system for antiphage resistance) provides immunity against bacteriophage. The pyrimidine cyclase (PycC) synthesizes cyclic nucleotides in response to infection; these serve as specific second messenger signals. The signals activate the adjacent effector, leading to bacterial cell death and abortive phage infection. A clade E Pycsar system. The effector component of a two-gene Pycsar system. Expression of this and adjacent cytidylate cyclase EcPycC (AC P0DV24) confers resistance to bacteriophage P1 and T5; this protein is required for resistance. When cells expressing the Pycsar system are infected by phage T5 at low multiplicity of infection (0.2 MOI) the culture survives, at 2.0 MOI bacteria enter growth arrest. The same cells enter growth arrest after exposure to 250 uM cCMP but not cUMP; this effector protein responds only to cCMP, usually produced by its cognate NTP cyclase. Some of the cells treated with cCMP have abnormal membrane protrusions, probably due to effects on membrane integrity. T5 phage that escape Pycsar have mutated major capsid protein pb8 (D20, AC Q6QGD8); infection with these phage elicits less cCMP production. Ectopic expression of the capsid protein in addition to both Pycsar genes does not induce effector-mediated toxicity, suggesting another factor is necessary.