The CRISPR/Cas immune system in *Streptococcus thermophilus* has been shown to naturally acquire spacers from both phage and plasmid DNA, leading to plasmid loss and phage resistance. The system targets double-stranded DNA within the proto-spacer region, cleaving it at specific sites. This activity is cas5-dependent and can be used to generate safer microbial strains by preventing the dissemination of antibiotic-resistant plasmids. The CRISPR/Cas system's ability to target and cleave invading DNA provides a natural mechanism for bacterial defense and could be exploited for biotechnological applications.The CRISPR/Cas immune system in *Streptococcus thermophilus* has been shown to naturally acquire spacers from both phage and plasmid DNA, leading to plasmid loss and phage resistance. The system targets double-stranded DNA within the proto-spacer region, cleaving it at specific sites. This activity is cas5-dependent and can be used to generate safer microbial strains by preventing the dissemination of antibiotic-resistant plasmids. The CRISPR/Cas system's ability to target and cleave invading DNA provides a natural mechanism for bacterial defense and could be exploited for biotechnological applications.