The E. coli CRISPR-Cas conundrum: are they functional immune systems or genomic singularities?

The discovery and subsequent characterization and applications of CRISPR-Cas is one of the most fascinating scientific stories from the past two decades. While first identified in Escherichia coli, this microbial workhorse often took a back seat to other bacteria during the early race to detail CRISPR-Cas function as an adaptive immune system. This was not a deliberate slight, but the result of early observations that the CRISPR-Cas systems found in E. coli were not robust phage defense systems as first described in Streptococcus thermophilus. This apparent lack of activity was discovered to result from transcriptional repression by the nucleoid protein H-NS. Despite extensive evidence arguing against such roles, some studies still present E. coli CRISPR-Cas systems in the context of anti-phage and/or anti-plasmid activities. Here, the studies that led to our understanding of its cryptic nature are highlighted, along with ongoing research to uncover potential alternative functions in E. coli.