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 an overall agreement in which antimicrobial resistance was identified as a growing concern, a “slow moving tsunami” (Dr Margaret Chan, WHO Director-General), and that we wanted to accept a challenging project which is achievable and will 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, 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 consumption 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.

Bacteria can develop resistance from mutations that cause the resistant bacterium to survive when the rest are killed, leaving the resistant bacterium to multiply and develop into a strain of resistant bacteria. By supplying 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. 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.

We believe our GM bacteria can be used in animal feed, a ‘BactiFeed’, to remove common bacterial infections in livestock. Post-Weaning Diarrhoea in pigs is commonly caused by E. coli in the gut, and leads to dehydration, loss of body weight and death of infected pigs. To prevent mass infections and loss of income, farmers will administer broad range antibiotics to the whole herd after one confirmed diagnosis, resulting in a massive overuse of the antibiotics. We believe our BactiFeed will act as both a preventative measure for pigs that are not infected, but also a treatment for pigs that have already contracted the infection. Due to the enormity of these consequences, we consulted a range of professionals to discuss their thoughts on our project.

To achieve our goal, we can pinpoint the most specific bacteriocins for each of the bacteria and ligate them into E. coli, along with pH sensitive and bile salt responsive transcription promoting machinery, which are activated at a low and high pH similar to conditions in the stomach and intestines, respectively, to stimulate bacteriocin production when consumed by livestock. To aid this, we can use mathematical modelling to determine the concentration of bacteria required per serving of BactiFeed to completely remove the bacterial infections in the chickens.