It’s projected that by 2050, 10 million people will die per year from diseases caused by antibiotic-resistant bacteria. That’s more than the current death rate due to cancer and diabetes combined, and will cost $100 trillion to treat.
The primary method for treating bacterial infections is antibiotics. Yet these deadly bacteria are rapidly acquiring antibiotic resistance genes, reducing the effectiveness of current medications and creating a need for alternative treatment strategies.
As part of an international competition, the Colorado State University International Genetically Engineered Machine (iGEM) team is leveraging expertise in synthetic biology to propose a solution to this prevalent health issue. The team is advised by Christie Peebles, associate professor in the Department of Chemical and Biological Engineering, and Claudia Gentry-Weeks, associate professor in the Department of Microbiology, Immunology, and Pathology.
An alternative to antibiotics
The iGEM team aimed their biologic expertise at a superbug called methicillin-resistant Staphylococcus aureus (MRSA), a type of bacteria that’s completely resistant to methicillin and all beta-lactam antibiotics such as penicillin and ampicillin. MRSA contains a group of genes encoding a mechanism called quorum sensing, which gives the bacteria the ability to sense their population density. Once the bacteria reach a critical mass, they’re poised to strike, as they require a large enough population to successfully cause disease in the host organism.
“Staphylococcus aureus needs a population of a certain size to cause disease in a host organism,” said Ryan Boudreau, senior biomedical and chemical and biological engineering student. “They can’t infect with too small of a population – they need to grow first.”
Using genetic modification, the team intends to extract the quorum sensing genes from MRSA and place them into a harmless form of E. coli bacteria. With this alteration, the E. coli bacteria will possess the ability to sense the population density of nearby MRSA. With further modification, the E. coli will be equipped with what’s called a bacteriophage, literally meaning “bacteria eater,” that will destroy the antibiotic-resistant bacteria just before they reach critical mass and initiate infection.
“The bacteriophage is like a virus, and there are some that specifically attack MRSA,” said Tyler Daniel, senior biomedical and chemical and biological engineering student. “A future goal for this project is to tailor the phage to attack other types of bacteria, too.”
The students are still working through development of the quorum sensing mechanism. They are making progress toward creating a functional MRSA bacteriophage that is produced when MRSA is detected – what they affectionately call the “kill switch.”
The multidisciplinary team, made up of students from three colleges and seven disciplines, presented their project at iGEM 2018 in October. They earned a bronze medal for their work. This was the first research lab experience for many of the students on the team.
A Senior Design group in the School of Biomedical Engineering will continue where the team left off, developing the quorum sensing mechanism using computer modeling. Next summer, the project will be passed back to the CSU iGEM team, who will present their progress at iGEM 2019.
This year the project was funded by the Walter Scott Jr. College of Engineering, the College of Veterinary Medicine and Biomedical Sciences, the Department of Microbiology, Immunology, and Pathology, and the Department of Chemical and Biological Engineering.
“iGEM was probably the best hands-on experience I’ve had in engineering,” said Boudreau. “It’s prepared me more for an industrial type of application than any other experience.”