Team:Oxford/Test/Project
[PROJECT]
overview
The World Health Organisation have recently (May 2015) endorsed a global action plan to tackle antimicrobial resistance.
Antimicrobial resistance is a complex problem driven by many interconnected factors. As such, single, isolated interventions have little impact. Coordinated action is required to minimize emergence and spread of antimicrobial resistance.
Our solution to antimicrobial resistance is to turn bacteria on themselves. Although bacteria are generally thought of as causing infection, most bacteria that live inside the human body are non-pathogenic and some of them can be turned, after proper engineering, into ‘smart’ living therapeutics that have the potential to treat a diverse range of diseases. We are focused specifically on treating urinary tract infections (UTIs). Resistance to one of the most widely used antibacterial drugs for the oral treatment of urinary infections caused by E. coli – fluoroquinolones – is now widespread and, with UTIs being the most commonly acquired infection at hospital, there is a huge need to find a solution for the treatment of UTIs and resistance to antimicrobial resistance.
How?
We are working on a novel antimicrobial strategy that uses engineered avirulent E. coli to treat UTIs, which are caused by uropathogenic bacteria and the biofilm that they form in the urinary tract. By employing engineered E. coli, we can create a system that offers persistent protection against biofilm formation in the urinary tract and on the surface of catheters without the use of antibiotics.
“While there is a lot to be encouraged by, much more work needs to be done to combat one of the most serious global health threats of our time.”
Dr Keiji Fukuda
WHO’s Assistant Director-General for Health Security
The project aims to investigate how bacterial biofilm disrupting proteins can be exported from E. coli. The proteins DispersinB, MicrocinS, DNase and Endolysin will be expressed from commercial pBAD expression vectors with N-terminal fusion tags to target them for export via the DsbA, YebF and flagellar export pathways in E. coli. Additionally, the holin gene will be expressed under the control of bacterial quorum sensing responsive promoters (in conjunction with the endolysin) to cause host cell lysis and release of these proteins from the cytoplasm on detection of a high target cell density.