Fig. 2. (A) Schematic of homologous recombination of phage receptor binding proteins to alter phage host target range. Modified from Lenneman et al. (2021). (B) Schematic of phage triggered CRISPR-Cas9 pathway for activation of endogenous bacterial nuclease via CRISPR RNA (crRNA). (1) Phage adsorbs to target bacterium and injects its genome into the cell. (2) Phage enters replication cycle, where spacers contained in the phage genomes CRISPR array are expressed and mature into crRNAs and phage structural proteins are produced. (3) The phage cRNAs guide endogenous Cas9 proteins to cut targeted loci in the bacterial genome and/or plasmids. (4) Cuts lead to cell death if the bacterium is unable to repair genome damage or re-sensitization to antibiotics if antibiotic resistance gene on plasmid is damaged. Phage completes its replication cycle and assembles new progeny virions, which lyse the cell and are released into surroundings. Modified from Fage et al. (2021).