The coordination of innate and adaptive immunity in bacteria

Abstract

ABSTRACTBacteria have evolved a variety of innate and adaptive immune strategies to fight bacteriophage (phage) infections. Innate defenses (unspecific mechanisms directed against any phage infecting the cell) range from the identification and cleavage of the viral DNA by restriction nucleases to the suicidal death of infected host cells, an extreme solution that prevents the spread of the infection throughout the population. Adaptive immunity, on the other hand, involves the creation of an immune memory that targets specific phages in case of reinfection. It is obvious that not every infection leads to the suicide of the host cell or to the formation of immune memory against the infecting phage, so what determines the outcome of an anti-phage response? In this work, we suggest that the dynamic aspects of phage infections are key to addressing this question. We show that the rates of viral DNA replication and cleavage define functional categories of phages that differ in their susceptibility to the immune strategies evolved by bacteria. From this viewpoint, the combined action of diverse bacterial defenses would be necessary to reduce the chances of phage immune evasion. This perspective allows us to formulate simple molecular mechanisms that could account for the decision of infected cells to undergo suicidal cell death or to incorporate new phages into the immune memory. This work highlights the importance of dynamics to understand bacterial immunity and formulates explicit hypotheses that could inspire a new and original empirical approach to the study of phage/bacteria interactions.