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 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.
Deaths attributable to AMR every year. Adapted from (1)
The report 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 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. 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.
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 reduces or eliminates 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. 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 an 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 our target bacteria. These bacteriocins will then be designed to be activated by pH sensitive and bile salt responsive promoters. These conditions simulate bacteriocin production in the stomach and intestines when our BactiFeed would be 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.
References
(1) AMR Review 2016. https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf
Aims of F.B.I : BactiFeed Is All You Need (Blue title )
1. To use synthetic biology to address the emerging problem of antibiotic resistance (add link to project design)
2. To use synthetic biology to improve the characterisation of a number of promoter including two pH sensitive promoters (BBa_ and BBa_) and a bile salt sensitive promoter (BBa_). We will clone gfp (
3. To use synthetic biology to create a number of modularised colicins which lack a cytotoxic domain (BBa_ and BBa_) in order to develop novel toxins with specific warheads (BBa_, BBa_BBa_)to target pathogenic bacteria. We will then test the heterologous expression of these toxins and their toxicity to target bacteria. Find out more (link to toxins part of results).
4. Mathematical modelling was carried out to aid in the understanding of our system and lead to further improvements. Find out more here (link to modelling page).
5. To build an easy to use piece of hardware, which we can use for our proof of concept experiments. The piece of hardware should be designed to exert mechanical stress on our samples in order to simulate a stomach environment. Find out more (link to hardware page).
6. Through every step of the way we have engaged with experts and the public to discuss our ideas and ensure that our product is tackling an unmet need. Find out more (link to human practices overview)
