Bacteriocin-Producing Probiotics as Precision Antimicrobial Therapeutics: From Lactic Acid Bacteria to Emerging and Engineered Next-Generation Platforms

Abstract

The emergence of antimicrobial resistance (AMR) has created a need for new, targeted alternatives to conventional antibiotics. Bacteriocins and other targeted antimicrobial peptides (AMPs) are emerging therapeutic approaches that have attracted attention for their potent antimicrobial properties and potential for more specific effects on microbial communities. The review describes the development of probiotics from lactic acid bacteria (LAB) to next-generation probiotics (NGPs), incorporating genomics, metagenomics, and synthetic biology to develop and engineer antimicrobial-producing microbial platforms. A comparative analysis of the bacteriocin profiles of conventional LAB and NGPs is presented, highlighting differences in diversity, specificity, and therapeutic potential. Additionally, recent advances in large-scale bacteriocin production systems, including recombinant expression and bioengineering methods, are discussed. Issues related to delivery systems, stability, host interactions, and targeted release are discussed. Most evidence comes from in vitro and animal studies, with limited clinical data on bacteriocin-producing probiotics and NGPs. There is also a significant gap in direct experimental proof of bacteriocin production by many proposed NGPs, hindering their development as targeted antimicrobials. Regulatory, scale-up, and manufacturing challenges remain major barriers to commercialization and broad therapeutic use. Target pathogen prioritization is a final step highlighted in the review that will help in therapeutic precision and improve the outcome of treatment for multidrug-resistant pathogens. Overall, LAB-derived bacteriocins have the most substantial evidence for production, characterization, and safety, while NGP-associated systems are promising but mostly preclinical and need further structural and functional validation. Moving towards precision antimicrobial therapy will depend on developing standardized activity assays, evaluating microbiome interactions, monitoring resistance, ensuring strain safety, establishing scalable manufacturing processes, and conducting comprehensive human clinical trials.