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Revision as of 17:41, 25 August 2019

<!DOCTYPE html> ProQuorum

The problem now

C. difficile infection (CDI) is the leading cause of hospital and nursing home acquired infection in the developed world. Today, nearly half of all hospitalised patients will be prescribed antibiotics. These antibiotics drastically alter the gut flora, and patients become more susceptible to opportunistic bacteria like C. difficile. Presently, patients over the age of 65 account for more than 80% of the deaths from C. difficile infection (CDI). Population ageing will inevitably increase the number of annual infections.

Our Solution

We hope to change these statistics with a new, revolutionary approach to C. difficile, which harnesses the power of probiotics and quorum sensing—ProQuorum. We are designing our ProQuorum bacteria to be super-probiotics. We are using Lactobacillus reuteri as our chassis which are naturally beneficial to the gut flora. These bacteria will be engineered to target any C. difficile present in the gut. Using quorum sensing, the ProQuorum bacteria will detect C. difficile and subsequently release a C. diff-specific endolysin to kill the C.difficile.

Why SynBio?

Synthetic biology allows for a specific, targeted approach, which should preserve the other beneficial gut bacteria. The ProQuorum detection system means C.diff-specific endolysin is only secreted when C.difficile is present and should only be able to destroy the C.difficile bacteria which should mitigate any off-target effects.

What was the inspiration for our project?

When we first started brainstorming for our project, many of us were concerned about the ever-looming threat of antibiotic resistance. When we looked into it, we discovered that the Centres for Disease Control (CDC) had cited Clostridioides difficile as one of the 3 most “urgent threats” with regard to antimicrobial resistance. Of the three, it has the highest incidence of infections per year (CDC, 2015). So we took it upon ourselves to respond to the CDC’s call to arms. In addition, we realised that the fundamental basis behind any genetic machine is to process some input and in response, provide some output. As such, we envisioned a genetic machine that could detect some biomarker of C. difficile and then as a result, secrete a specific anti-C.difficile molecule, as we have designed.

So how bad is c.dificile?

There are typically 500,000 infections per year in the US alone. C. difficile infection (CDI) places a major burden on healthcare systems around the world with extra costs of around $4.8 billion p.a. In the US alone, it is linked to approximately 30,000 deaths per year (CDC, 2015) Additionally, CDI has a relatively high frequency of recurrence of approximately 20%-30% (Balsells et al. 2018). This makes it significantly more troublesome to treat, especially with regards to the proliferation of resistant strains. Furthermore, the formation of spores which are resistant to heat, acid, antibiotics and even bleach allows C. difficile a pathway through which it can survive antibiotic treatment and then spread to other individuals. Such spores are “plentiful in healthcare facilities” (Leffler et al. 2015) contributing to the patient-to-patient spread and recurrence rate.

How does our system work?

Engineered Lactobacillus reuteri (ProQuorum bacteria) to function as a genetic machine characterised by i) Input: Quorum sensing molecule of C.difficile ii) Output: C. difficile-specific endolysin Thus, our engineered bacteria can detect the localised presence of C. difficile and in response, secrete an endolysin molecule which specifically binds to C. difficile cell walls and cleaves the peptidoglycan molecules to cause lysis of the C. difficile cells.

Our Project

We have approached our project from many angles, the links to these sections will appear as summer goes on