Difference between revisions of "Team:Dundee/Design"
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<p>Figure 4.Illustration of our proof of concept. Our bacteria producing our synthetic toxins will be expressed in the presence of low pH and then the cells will lyse and release the synthetic toxins in response to bile salts. </p> | <p>Figure 4.Illustration of our proof of concept. Our bacteria producing our synthetic toxins will be expressed in the presence of low pH and then the cells will lyse and release the synthetic toxins in response to bile salts. </p> | ||
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Revision as of 00:33, 19 October 2016
Project Design
How BactiFeed Works
Bacteriocins modified to target specific bacteria
From Farm to Fork...
Food security within the agricultural environment is what we are targeting, in particular focusing on bacterial infections within livestock and drug resistance. Food security begins right at the beginning of the production line: at the farm. The industrialisation of animal production was made possible by the availability of antibiotics for livestock and poultry. The livestock must be kept healthy in order to reach food security standards, not only is this important to the agricultural environment but it also means a healthy economy for the farming industry. Antibiotics are currently used in feed to protect livestock from infections as well as to generally boost their growth, however drug resistance is causing large problems and the more antimicrobials are abused the worse the situation gets.
Figure 1. Misuse of antibiotics in livestock can have many downstream effects, including the increased potential of the emergence of resistant human pathogens. Fig from (1)
Discovery of new antibiotics is at an all-time low; it has been 30 years since a new class of antibiotics was last introduced. Only 3 of the 41 antibiotics in development have the potential to act against the majority of the most resistant bacteria.
Our mission is to use synthetic biology in order to solve this problem and to create an array of novel toxins by modularising the architecture of bacteriocins.
Figure 2. Timeline showing the date of discovery of antibiotics and the date of resistance. (2)
We will be focussing on a specific set of bacteriocins known as colicins. Colicins are bacteriocins produced by E. coli and are proteins produced and secreted by bacteria in order to eliminate closely related competitor strains. We aim to generate novel toxins by alternating the cytotoxic domains with different warheads. This gives us the ability to design selective toxic domains targeting only pathogenic strains. This approach has a great advantage over antibiotics, which are often rather non-selective. The livestock produce can now pass the food security standards without impacting global antimicrobial resistance and land safely on the consumer’s fork.
Figure 3. Colicin structure showing the three domains of a colicin. Possibility of interchanging the toxic domains (Warheads) at the multiple cloning site of bacteriocin structure allows for less chance of resistance and more specificity.
...And From Beak to Bum
Our idea was to create a feed for livestock (in this case we focused on chickens), which is coated in our synthetic colicin producing bacteria. This is BactiFeed. The concept is simple; the chickens eat BactiFeed, as the bacteria travel through the GI tract of the chicken they begin to produce these synthetic colicins. The colicins are not active when expressed in the host cell as the host expresses a corresponding immunity protein to the colicin. In order to release the colicins to allow them to target unwanted bacteria the producing cells must lyse.
Figure 1. Misuse of antibiotics in livestock can have many downstream effects, including the increased potential of the emergence of resistant human pathogens. Fig from (1)
Figure 4.Illustration of our proof of concept. Our bacteria producing our synthetic toxins will be expressed in the presence of low pH and then the cells will lyse and release the synthetic toxins in response to bile salts.
