Difference between revisions of "Team:Oxford/Description"

What?

The threat of antimicrobial resistance is a serious global public health concern. One of the ways bacteria protect themselves against antimicrobial drugs is by growing biofilms. The biological definition for a biofilm: “an assemblage of surface-associated microorganisms that secrete a mucilaginous protective coating in which they are encased.” Van Leeuwenhoek, using his simple microscopes, first observed microorganisms on tooth surfaces and can be credited with the discovery of microbial biofilms. These bacterial slimes are responsible for a whole host of medical, industrial and environmental problems that are very costly and technically challenging to remedy. Biofilms are involved in catheter and implant infections, dental plaque formation as well as infections in cystic fibrosis patients. Biofilm can be found in the urothelium, prostate stones, and implanted foreign bodies. In industry and infrastructure, biofilms are also the main culprit behind the fouling of various plants and pipelines for aquaculture, water treatment, and food production.

Our solution is focused on providing a treatment for urinary tract infections (UTIs). 90% of urinary infections are caused by uropathogenic E. coli (UPEC) and the biofilm that they form in the urinary tract. 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.

See UTIs facts and figures for more information.

Both antimicrobial resistance and the other problems associated with biofilm formation are big issues in their own right but are especially problematic when they’re combined. The bacteria, already constantly evolving to afford themselves more innate resistance against antibiotics, produce biofilms as protective layers that shield them from the drugs even more comprehensively.

Why?

• UTIs are the most common nosocomial infection
• There is growing resistance to the antibiotics currently used to treat urinary infections
• Biofilms are major problem both in health and industry
• Antibiotics have a negative effect on the beneficial gut flora
• There is a current failure to prevent recurrent infections

How?

There is currently no commercial antibiotic that specifically targets bacterial biofilms, but researchers have identified a range of bacterially-derived biomolecules that degrade and destroy biofilms. Our solution aims to investigate how bacterial biofilm disrupting proteins and antimicrobial proteins can be exported from E. coli.

The proteins DispersinB, MicrocinS, DNase and Endolysin will be fused with secretion tags to target them to normal bacterial secretion pathways. By hijacking the natural processes by which E. coli secrete proteins, we can target our anti-biofilm agents out of E. coli and onto a biofilm infected surface. Additionally, our E. coli will lyse upon sensing the presence of a biofilm, releasing a pulse of proteins from the cytoplasm on detection of a high target cell density.

The beauty of the anti-biofilm agents we plan to use is that they have been shown not to induce resistance in the target bacteria, meaning that having them continually produced at a low level will not be nearly bad as with traditional antibiotics. Our system is applicable to a whole host of biofilm environments and with a simple design that can be used in multiple sectors, we hope to get a step further in providing a novel approach to treating microbial infections. In terms of product formulation and design, we hope to ultimately arrive at a functional proof-of-concept e.g. an enzyme-secreting infection-clearing catheter or a modular system that continuously and cheaply cleans out pipelines.