Precise and controllable Live Bacteria Therapeutics

The human body is host to diverse microbial communities, and the complex interactions between the host and its microbial counterparts play a key role in human health and disease. How to utilize complex interactions between microbial communities and hosts to treat diseases, such as inflammation and tumor, become a new therapeutic strategy. The idea of Live Bacteria Therapeutics (LBTs) is to engineer bacterial chassis to produce therapeutics that are able to repair or restore healthy microbial function and diversity. Existing efforts have primarily focused on engineering probiotic bacterial strains from the Bacteroides or Lactobacillus families or Escherichia coli from labs. One challenge of using engineered probiotics as the next genereation therapy is to realize precise diagnosis and controllable treatment. Therefore, engineered protbiotics should sense inflammation region or pathogens and only release certain amount of drugs, and induce exiting or self-killing mechanisms for biocontainment.
Precise control of engineered probiotics on h. pylori infection. A. Sketch of engineered probitics interacting with pathogen h. pylori. B. Engineered probiotics include feedback control circuits of sensing, computation and therapy components.
We are intereted in one highly harmful pathogen, Helicobacter pylori (h. pylori), which directly leads to stomach cancer. The pathogen h. pylori can survive the acidic environment and implant in human stomach and release toxins that induce severe diseaese. Traditional treatment uses antibiotics for h. pylori eradication, yet it becomes less efficient due to the resistence of h. pylori and causes dysbiosis of the gut microbiota. Therefore, we are looking for engineered probiotics that are specifically designed to eradicate h. pylori while not interfering with other healthy microbiome. To realize precise and controllable treatment, we need to design feedback control circuit in probiotics that can sense the existence of h. pylori, decide if certain amount of drugs need to be released, and check the therapeutics effect and turn on exiting or self-killing procedure.