The CRISPR/Cas system in bacteria and archaea defends against foreign nucleic acids like viral genomes and plasmids. It consists of CRISPR loci and associated Cas genes, which store spacers from extrachromosomal elements. These spacers enable sequence-specific immunity against phages and plasmids. In *Streptococcus thermophilus*, the CRISPR1/Cas system can acquire spacers from a self-replicating plasmid containing an antibiotic resistance gene, leading to plasmid loss. Acquired spacers that match antibiotic resistance genes help naturally select bacteria that cannot uptake and spread such genes. The CRISPR/Cas system specifically cleaves plasmid and phage double-stranded DNA within the proto-spacer at specific sites. This activity was demonstrated in *S. thermophilus* by showing that the system can target and cut plasmid DNA, leading to plasmid instability. The system also targets phage DNA, cleaving it within the proto-spacer, which provides resistance against phage infections. The CRISPR/Cas system in *S. thermophilus* acts in two stages: adaptation, where new spacers are acquired from foreign DNA, and interference, where the system targets invading DNA or RNA. The interference stage involves transcription of the CRISPR locus, processing into CRISPR RNAs, and using them to guide the Cas proteins to cleave foreign DNA. The study shows that the CRISPR/Cas system can cause plasmid loss in *S. thermophilus* by integrating spacers from plasmids, leading to plasmid instability. It also demonstrates that the system can target and cleave plasmid and phage DNA, providing a natural mechanism to prevent the spread of antibiotic resistance genes. The system's ability to cleave DNA at specific sites within the proto-spacer is crucial for its function. The CRISPR/Cas system in *S. thermophilus* is a key defense mechanism against phages and plasmids, contributing to the natural scarcity of plasmids in wild-type strains. It can be harnessed to generate safer microbial strains with increased phage resistance and reduced plasmid dissemination. The system's activity was confirmed through various experiments, including plasmid stability assays, Southern hybridizations, and direct sequencing of cleavage sites. The findings highlight the CRISPR/Cas system's role in bacterial immunity and its potential applications in biotechnology.The CRISPR/Cas system in bacteria and archaea defends against foreign nucleic acids like viral genomes and plasmids. It consists of CRISPR loci and associated Cas genes, which store spacers from extrachromosomal elements. These spacers enable sequence-specific immunity against phages and plasmids. In *Streptococcus thermophilus*, the CRISPR1/Cas system can acquire spacers from a self-replicating plasmid containing an antibiotic resistance gene, leading to plasmid loss. Acquired spacers that match antibiotic resistance genes help naturally select bacteria that cannot uptake and spread such genes. The CRISPR/Cas system specifically cleaves plasmid and phage double-stranded DNA within the proto-spacer at specific sites. This activity was demonstrated in *S. thermophilus* by showing that the system can target and cut plasmid DNA, leading to plasmid instability. The system also targets phage DNA, cleaving it within the proto-spacer, which provides resistance against phage infections. The CRISPR/Cas system in *S. thermophilus* acts in two stages: adaptation, where new spacers are acquired from foreign DNA, and interference, where the system targets invading DNA or RNA. The interference stage involves transcription of the CRISPR locus, processing into CRISPR RNAs, and using them to guide the Cas proteins to cleave foreign DNA. The study shows that the CRISPR/Cas system can cause plasmid loss in *S. thermophilus* by integrating spacers from plasmids, leading to plasmid instability. It also demonstrates that the system can target and cleave plasmid and phage DNA, providing a natural mechanism to prevent the spread of antibiotic resistance genes. The system's ability to cleave DNA at specific sites within the proto-spacer is crucial for its function. The CRISPR/Cas system in *S. thermophilus* is a key defense mechanism against phages and plasmids, contributing to the natural scarcity of plasmids in wild-type strains. It can be harnessed to generate safer microbial strains with increased phage resistance and reduced plasmid dissemination. The system's activity was confirmed through various experiments, including plasmid stability assays, Southern hybridizations, and direct sequencing of cleavage sites. The findings highlight the CRISPR/Cas system's role in bacterial immunity and its potential applications in biotechnology.