Team:Dundee/Description

Project Description

BactiFeed

A novel solution to antimicrobial resistance?

Project Description

We are the undergraduate iGEM team from the University of Dundee and we’re Fighting Bacterial Infections.

Our project has developed from a team agreement in which we decided to work on antimicrobial resistance. The issue of antimicrobial resistance was identified as a growing concern, a “slow moving tsunami” (Dr Margaret Chan, WHO Director-General). We wanted to accept a challenging project which was achievable and would deliver a positive impact on a global crisis. The Review on Antimicrobial Resistance, commissioned by the UK Government and chaired by Lord Jim O’Neill predicted that by 2050 antimicrobial resistance will become one of the biggest killers exceeding cancer (Fig 1). It was also found that there was poor surveillance and data collection in most countries, however it is clear that the use of antibiotics in agriculture is widespread on a scale at least equivalent to use in humans, and it is projected to increase. Van Beockel et al. (2015) estimate that usage of antibiotics in agriculture will increase to 67% globally by 2030, and to 99% in Brazil, Russia, India, China and South Africa. Further, more than 70% of antibiotics deemed medically important for human health by the FDA sold in the United States are used in livestock, with most other countries above 50%. Clearly, the use of antibiotics has escalated to unsustainable levels and an alternative must be found.

Figure 1. Deaths attributable to AMR every year. Adapted from ⁽¹⁾

The Review also highlighted ten areas that they believed could have a huge impact on reducing the threat of antimicrobial resistance (Fig 2). Our team chose to research more about the effects of antibiotics in agriculture and the environment. We found that antimicrobial resistance in livestock also poses a Food Security issue. The quantity of antibiotics used in livestock is vast. In the US, for example, of the antibiotics defined as medically important for humans by the US Food and Drug Administration (FDA), over 70 percent (by weight) are sold for use in animals. Too many antibiotics that are now last-line drugs for humans are being used in agriculture.

Figure 2. Tackling antimicrobial resistance on ten fronts. We focused our attention on reducing antibiotics in agriculture and the environment. Adapted from ⁽¹⁾

Project Description

Antibiotic resistance occurs when bacteria develop mutations that reduce or eliminate the effectiveness of drugs, chemicals, or other agents designed to cure or prevent infections. The bacteria survive and continue to multiply causing more harm. By continuously using more antibiotics, we kill off any competition for these resistant strains and provide them with more resources to multiply. A bacterial strain can then pass resistant genes to a non-resistant strain, creating more resistant strains that thrive without competition. Clearly, a new method for removing bacterial infections is required.

Our team is displaying a method to combat specific bacterial infections without antibiotics, using proteins called bacteriocins that are secreted naturally by bacteria to kill similar strains in order to reduce competition (Fig 3). . We are engineering non-pathogenic E. coli to produce bacteriocins that will kill pathogenic strains of E. coli and similar bacteria such as Salmonella - these are just two examples of how our method works.

Figure 3. Schematic illustrates the competition between a target bacteria and an attacker cell. The attacker delivers a toxic effect through the release of bacteriocins and the uptake of these into the target cell. Bacteriocins contain three domains: translocation domain (orange), receptor binding domain (yellow) and a cytotoxic domain (blue). 1. Synthesis of bacteriocin and binding to its cognate immunity protein for protection of the host cell. 2. Release of the bacteriocin either through secretion or cell lysis. 3. Binding of bacteriocin to specific receptors on the target cells, and translocation of the toxic domain into the correct compartment for toxicity. 4. Toxic effect delivered resulting in death of target bacteria.