Curr Biol：细菌的天然CRISPR免疫防御机制

Edze R. Westra5, Stineke van Houte5, Sam Oyesiku-Blakemore, Ben Makin, Jenny M. Broniewski, Alex Best, Joseph Bondy-Denomy, Alan Davidson, Mike Boots, Angus Buckling

In the face of infectious disease, organisms evolved a range of defense mechanisms, with a clear distinction between those that are constitutive (always active) and those that are inducible (elicited by parasites) [ 1 ]. Both defense strategies have evolved from each other [ 2 ], but we lack an understanding of the conditions that favor one strategy over the other. While it is hard to generalize about their degree of protection, it is possible to make generalizations about their associated fitness costs, which are commonly detected [ 3–5 ]. By definition, constitutive defenses are always “on,” and are therefore associated with a fixed cost, independent of parasite exposure [ 4, 5 ]. Inducible defenses, on the other hand, may lack costs in the absence of parasites but become costly when defense is elicited [ 6 ] through processes such as immunopathology [ 7 ]. Bacteria can evolve constitutive defense against phage by modification/masking of surface receptors [ 8, 9 ], which is often associated with reduced fitness in the absence of phage [ 10 ]. Bacteria can also evolve inducible defense using the CRISPR-Cas (clustered regularly interspaced short palindromic repeat, CRISPR associated) immune system [ 11 ], which is typically elicited upon infection [ 12–14 ]. CRISPR-Cas functions by integrating phage sequences into CRISPR loci on the host genome [ 15 ]. Upon re-infection, CRISPR transcripts guide cleavage of phage genomes [ 16–20 ]. In nature, both mechanisms are important [ 21, 22 ]. Using a general theoretical model and experimental evolution, we tease apart the mechanism that drives their evolution and show that infection risk determines the relative investment in the two arms of defense.