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Abstract
CRISPR (clustered regularly interspaced short palindromic repeat) arrays and Cas(CRISPR-associated) proteins provide bacteria and archaea with immunity against phages
and other mobile genetic elements (MGEs). The immunity provided by CRISPR-Cas
systems is adaptive as sequences are acquired from invaders and stored in the CRISPR
array, capable of guiding sequence-specific nuclease activity during future encounters. In
response, phages and other MGEs encode anti-CRISPR proteins that inhibit the defense of
CRISPR-Cas immunity. This dissertation begins with characterization of CRISPR-Cas
systems in Streptococcus thermophilus with an emphasis on Type III-A systems. It then
explores anti-CRISPR protein prediction in phages of S. thermophilus followed by
screening and identification of novel CRISPR-Cas inhibitors. The final chapter focuses on
the selectivity of spacer targeting against S. thermophilus phage genes with potential
implications for our understanding of Type III-A CRISPR-Cas system function. The results
increase predictability of outcomes of phage-host encounters by expanding the repertoire
of known anti-CRISPR proteins and illuminating unique features and potential roles of
cooccurring CRISPR-Cas systems.