Team:Baltimore BioCrew/Entrepreneurship

Entrepreneurship



Antibiotics

According to the CDC, 4 out of 5 Americans are prescribed antibiotics every year. These antibiotics, while often lifesaving, can also lead to severe unintended health consequences. Antibiotics kill or slow the growth of any bacteria they encounter by destroying the cell wall or inhibiting protein production and reproduction. However, antibiotics kill not only the pathogens they were prescribed to destroy, but also many of the one trillion other resident bacteria that live peacefully in our gut. These non-pathogenic, helpful bacteria are a part of our microbiome, and help to digest food, control the immune system, synthesize needed vitamins, and produce neurotransmitters. Antibiotics decrease gut diversity by 25 percent, throwing the microbiome out of balance. This can lead to a range of health issues, including colitis, irritable bowel syndrome, and Crohn’s disease, while also increasing the risk for future infections by weakening the immune system and giving pathogens the space to grow.



MAFF

The way to avoid these consequences is to repopulate the gut to its original state as quickly after treatment as possible. In our body, microbiome diversity is regulated and encouraged by proteins called Mucus Associated Functional Factors (MAFFs). MAFFs are produced by B. theta, a bacterium that is easily destroyed by antibiotics. Thus, antibiotics reduce MAFF production, creating a feedback loop that prevents the reestablishment of a healthy gut.



Solution

By introducing E. coli that has been engineered to produce MAFFs into the gut, along with a xylose supplement, a stable microbiome could be regrown. This is achieved by altering the B. theta MAFF-producing gene and inserting it into the plasmid of E. coli. Because the bacteria will be delivered inside the human body, it is imperative that they contain a killswitch. This will prevent them from overpopulating and unbalancing the gut. Our killswitch, which we’re calling Order 66, releases a toxin when the bacteria are deprived of xylose. Once the bacteria use up their xylose supplement, they will die, but even with a short life expectancy, the E. coli will provide the MAFF needed to jump-start the reestablishment of a healthy microbiome.