Bacteriocins from interbacterial warfare as antibiotic alternative

Antimicrobial resistance (AMR) is an ongoing global crisis exacerbated by lack of discovery of novel antimicrobials and absence of investment/innovation in pipelines by the pharmaceutical industry. New alternatives that are target-specific and do not cause collateral damage to the microbiome would revolutionise human and animal health. Bacteriocins are small antibacterial peptides produced by bacteria that are gene-encoded and can be narrow or broad spectrum. They have potential for development of new antimicrobial molecules through discovery and protein engineering resulting in potent, targeted antimicrobials. They have many possible applications including treatment of gut and topical infections, and microbiome editing. However, basic research issues stand in the way of their exploitation including low production levels often in unsuitable hosts, resistance development in bacterial targets, and inadequate potency/inhibition spectrum. The main aim of BACtheWINNER is to develop bacteriocins as novel antimicrobials by solving these challenges through combining and innovating state-of-the-art technologies in peptide bioengineering and molecular genetics, which will lay the foundation for the generation of this new family of therapeutics that target WHO and CDC priority pathogens and undesirable microbiota. To achieve this, a four-phase bacteriocin discovery and development pipeline will be implemented which takes new and existing bacteriocins and improves them through bioengineering, develops optimal combinations, (over-)produces them in desirable hosts, and validates their use in preclinical models of human infection and disease. This will pave the way for their development as precision microbiome tools and antimicrobials against AMR pathogens. We bring together unique expertise necessary to deliver this project by combining bacteriocin and microbiome research with genetic manipulation of food and gut bacteria.