Our immune systems protect our bodies from foreign invaders. They detect, fight, and eradicate bacteria, viruses, fungi, and parasites. Sometimes this isn’t enough and the immune system harms what it was supposed to protect. Sometimes, people get sepsis.
Sepsis is a condition caused by the overreaction of the immune system to an infection. Common bacterial infections that lead to sepsis consist of: Enterococcus species, Escherichia coli, and Pseudomonas aeruginosa.
In the events leading to sepsis, the immune system produces cytokines which are signals that tell the body where to send immune cells to fight the infection. To allow more cells to travel through the body, the cytokines will dilate the blood vessels which decreases blood pressure resulting in reduced blood supply to organs.
The reduced blood supply and lack of adequate oxygen can cause tissue death and organ failure.
The detection of a bacterial membrane molecule initiates the immune response. This portion, endotoxin lipid A, is found in gram-negative bacteria cell membranes or free-floating once bacteria cells are lysed.
Sepsis is commonly treated using antibiotics. While these kill the bacteria, they ignore the lipid A molecule entirely, leading to a continued immune system response.
Phages are targeted phighters that only infect certain types of bacteria. We are using our phage to carry engineered DNA that can transcribe proteins that competitively bind or modify lipid A so the immune system does not detect it.
With our knowledge of molecular genetics and bacteriophages we found an application for synthetic biology in designing a treatment to combat sepsis.