Bacteriocins from interbacterial warfare as antibiotic alternative

Introduction

Antimicrobial resistance (AMR) is an ongoing global crisis exacerbated by the lack of discovery of novel antimicrobials and the 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 revolutionize human and animal health.

Bacteriocins Overview

Bacteriocins are small antibacterial peptides produced by bacteria that are gene-encoded and can be narrow or broad spectrum. They have potential for the development of new antimicrobial molecules through discovery and protein engineering, resulting in potent, targeted antimicrobials.

Applications of Bacteriocins

They have many possible applications including:

• Treatment of gut and topical infections
• Microbiome editing

Challenges in Bacteriocin Exploitation

However, basic research issues stand in the way of their exploitation, including:

1. Low production levels often in unsuitable hosts
2. Resistance development in bacterial targets
3. Inadequate potency/inhibition spectrum

Project Aim

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. This will lay the foundation for the generation of this new family of therapeutics that target WHO and CDC priority pathogens and undesirable microbiota.

Development Pipeline

To achieve this, a four-phase bacteriocin discovery and development pipeline will be implemented, which includes:

1. Taking new and existing bacteriocins and improving them through bioengineering
2. Developing optimal combinations
3. (Over-)producing them in desirable hosts
4. Validating 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.

Expertise and Collaboration

We bring together unique expertise necessary to deliver this project by combining bacteriocin and microbiome research with genetic manipulation of food and gut bacteria.