@Article{ValeEtal2015,
  URL = {pub/ValeEtal2015.pdf},
  Author = {Vale, P. F. and Lafforgue, G. and Gatchitch, F. and Gardan, R. and 
Moineau, S. and Gandon, S.},
  Title = {Costs of {CRISPR}-{C}as mediated resistance in {S}treptococcus 
thermophilus},
  Journal = {Proceedings of the Royal Society of London B},
  Volume = {282},
  number = {1812},
  Pages = {20151270},
  year = {2015},
  doi = {10.1098/rspb.2015.1270},
  abstract = {CRISPR-Cas is a form of adaptive sequence-specific immunity in 
microbes. This system offers unique opportunities for the study of coevolution 
between bacteria and their viral pathogens, bacteriophages. A full 
understanding of the coevolutionary dynamics of CRISPR-Cas requires knowing 
the magnitude of the cost of resisting infection. Here, using the gram-
positive bacterium Streptococcus thermophilus and its associated virulent 
phage 2972, a well-established model system harbouring at least two type II 
functional CRISPR-Cas systems, we obtained different fitness measures based on 
growth assays in isolation or in pairwise competition. We measured the fitness 
cost associated with different components of this adaptive immune system: the 
cost of Cas protein expression, the constitutive cost of increasing immune 
memory through additional spacers, and the conditional costs of immunity 
during phage exposure. We found that Cas protein expression is particularly 
costly, as Cas-deficient mutants achieved higher competitive abilities than 
the wild-type strain with functional Cas proteins. Increasing immune memory by 
acquiring up to four phage-derived spacers was not associated with fitness 
costs. In addition, the activation of the CRISPR-Cas system during phage 
exposure induces significant but small fitness costs. Together these results 
suggest that the costs of the CRISPR-Cas system arise mainly due to the 
maintenance of the defence system. We discuss the implications of these 
results for the evolution of CRISPR-Cas-mediated immunity.}
}