In clinical periodontal practice, patients with periodontitis frequently yield subgingival pathogens, resistant to therapeutic concentrations of commonly used antibiotics. The oral cavity is believed to provide excellent exogenous horizontal DNA transfer in dental plaque bacteria. Plasmids harness the replication, transcription, and translation systems of their host to ensure their continuity. While doing so, they burden their hosts' functionality. The non-specificity and inefficiency of current antibiotics and plasmid-mediated drug resistance is a major emerging challenge in dentistry.