RT Journal Article T1 The coordination of anti-phage immunity mechanisms in bacterial cells A1 Fernández Arias, Clemente A1 Acosta, Francisco J. A1 Bertocchini, Federica A1 Herrero García, Miguel Ángel A1 Fernández Arias, Cristina AB Bacterial cells are equipped with a variety of immune strategies to fight bacteriophage infections. Such strategies include unspecific mechanisms directed against any phage infecting the cell, ranging from the identification and cleavage of the viral DNA by restriction nucleases (restriction-modification systems) to the suicidal death of infected host cells (abortive infection, Abi). In addition, CRISPR-Cas systems generate an immune memory that targets specific phages in case of reinfection. However, the timing and coordination of different antiviral systems in bacterial cells are poorly understood. Here, we use simple mathematical models of immune responses in individual bacterial cells to propose that the intracellular dynamics of phage infections are key to addressing these questions. Our models suggest that the rates of viral DNA replication and cleavage inside host cells define functional categories of phages that differ in their susceptibility to bacterial anti-phage mechanisms, which could give raise to alternative phage strategies to escape bacterial immunity. From this viewpoint, the combined action of diverse bacterial defenses would be necessary to reduce the chances of phage immune evasion. The decision of individual infected cells to undergo suicidal cell death or to incorporate new phage sequences into their immune memory would be determined by dynamic interactions between the host’s immune mechanisms and the phage DNA. Our work highlights the importance of within-cell dynamics to understand bacterial immunity, and formulates hypotheses that may inspire future research in this area. PB Nature SN 2041-1723 YR 2022 FD 2022-06-22 LK https://hdl.handle.net/20.500.14352/113911 UL https://hdl.handle.net/20.500.14352/113911 LA eng NO Arias, C.F., Acosta, F.J., Bertocchini, F. et al. The coordination of anti-phage immunity mechanisms in bacterial cells. Nat Commun 13, 7412 (2022). https://doi.org/10.1038/s41467-022-35203-7 DS Docta Complutense RD 14 jun 2025