Bacteriocins as Targeted Microbiome Modulators: From Interbacterial Competition to Therapeutic Potential

Bacteriocins are ribosomally synthesized antimicrobial peptides produced by bacteria to inhibit or eliminate closely related competing microorganisms. In contrast to traditional broad-spectrum antibiotics, bacteriocins can be narrow-spectrum, allowing them to selectively affect a particular group of bacteria but leave the beneficial organisms of the microbiota intact. This accuracy has spawned increased interest in bacteriocins as possible reducers of microbial communities in the natural and clinical environment. Recent developments in the fields of genomics, metagenomics, and genome-mining tools have proved particularly useful in the process of the identification of novel bacteriocins, as well as in the discovery of their ubiquitous presence in heterogeneous bacteria. These peptides have a significant ecological role in microbial competition, niche competition, and community stability in complex ecosystems such as the human gut and food fermentation systems as well as environmental microbiomes. At the mechanistic level, bacteriocins use various strategies such as membrane pore formation, prevention of cell wall biosynthesis, nucleic acid degradation, and disruption of vital cellular enzymatic pathways. These multidimensional mechanisms may reduce the frequency and stability of resistance development compared with conventional antibiotics; however, adaptive resistance mechanisms may still emerge. There is mounting evidence to suggest that bacteriocins can redefine microbial population dynamics and can be used to redesign dysbiotic microbiomes linked to infection, metabolic and inflammatory diseases. Moreover, current developments in peptide engineering, synthetic biology, and heterologous expression systems are allowing the development of bacteriocins that are more stable, specific, and therapeutic. Bacteriocins can potentially be engineered to overcome certain resistance mechanisms. By manipulating microbial communities, they are reported to impact host physiology and affect neurochemical pathways. This review also reveals the ecological roles of bacteriocins in interbacterial competition, their new applications as specific microbiome regulators, and the existing advances toward their development as next-generation antimicrobial and microbiome-targeted therapies.