Synthetic biology approaches to antimicrobial resistance

Harnessing biological mechanisms to design useful functions is a central goal of synthetic biology.  As an Allen Distinguished Investigator, Jim Collins will explore novel technologies for manipulating gene circuits to confer designed advantages in antimicrobial therapies. 

The Centers for Disease Control reports that the rise of antibiotic resistance has become a public health crisis, leading to over two million infections and 23,000 deaths per year in the United States alone. The broad-spectrum antibiotics frequently employed to combat infection can serve to exacerbate resistance, since they clear out microbial niches and enable colonization by opportunistic pathogens.

Because resistant bacteria are so rapidly transmitted, our present ability to develop additional small-molecule therapeutics, broad spectrum or otherwise, is challenged. We need novel approaches and methodologies to keep up with the pace of resistance and address this growing crisis.

Synthetic biologists use tools and principles of engineering to program biological systems, and are increasingly able to draw on the natural diversity of sensors and regulators employed by living organisms to monitor and respond to their environments.

This work will engineer and rewire microbial circuits to create synthetic microbes capable of sensing and responding to bacterial pathogens—in essence, designing bacteria to fight dangerous infections.

Engineered bacteria that are recognized as safe and consumed around the world will be used first to target methicillin-resistant Staphylococcus aureus, or MRSA, the most frequently identified drug-resistant pathogen in U.S. hospitals. The engineered bacteria will express multiple novel lantibiotic peptides, which have been shown to be effective in controlling MRSA infections.

Another application of synthetic biology can combat antibiotic resistance in general, by engineering genetic elements that can remove the genes that enable bacteria to resist drugs. This strategy will use genetic cassettes that rapidly target and eradicate resistance genes from a microbial community.

Given the growing antibiotic crisis, it is also critical to understand the fundamental mechanisms by which antibiotics act and resistance arises. The work will develop a suite of synthetic biology tools to examine how drug resistance arises in bacteria, to study the dynamic effects of antibiotics in vivo, and discover novel antibiotics and antibacterial targets.

Affiliated Investigators

James J. Collins, Ph.D.

Massachusetts Institute of Technology

James J. Collins is the Termeer Professor of Medical Engineering & Science and Professor of Biological Engineering at MIT, as well as a Member of the Harvard-MIT Health Sciences & Technology Faculty. He is also a Core Founding Faculty member of the Wyss Institute for Biologically Inspired Engineering at Harvard University, and an Institute Member of the Broad Institute of MIT and Harvard. His research group works in synthetic biology and systems biology, with a particular focus on using network biology approaches to study antibiotic action, bacterial defense mechanisms, and the emergence of resistance. Professor Collins' patented technologies have been licensed by over 25 biotech, pharma and medical devices companies, and he has helped to launch a number of companies, including Sample6 Technologies, Synlogic and EnBiotix. He has received numerous awards and honors, including a Rhodes Scholarship, a MacArthur "Genius" Award, an NIH Director's Pioneer Award, as well as several teaching awards. Professor Collins is an elected member of all three national academies—the National Academy of Sciences, the National Academy of Engineering, and the National Academy of Medicine—as well as the American Academy of Arts & Sciences and the National Academy of Inventors.