MIT Team Tackles Drug-Resistant Superbugs
A team of Massachusetts Institute of Technology (MIT) engineers announced that they are addressing antibacterial resistance with the help of two new technologies developed at MIT.
According to the latest update from the World Health Organization, antimicrobial resistance (AMR) is an increasingly serious threat to global public health and threatens the effective prevention and treatment of infections. AMR is already found all around the world with new resistance mechanisms emerging and spreading. Also known as ‘superbugs’, drug resistant bacterial infections such as staphylococcus and multidrug-resistant tuberculosis (MDR-TB) infect over 2 million people and kill 23,000 in the U.S. However, discovery and development of a new class of antibiotics have lagged behind in the last ten years.
Led by Timothy Lu, associate professor of biological engineering and electrical engineering and computer science at MIT, the team of researchers have come up with a new answer to the increasing threat of antimicrobial resistance. The team developed the CRISPR genome-editing system and CombiGEM technology as potential treatments against drug-resistant superbugs. CRISPR is comprised of a set of proteins used by bacteria as a shield against bacteriophages. The engineers designed CRISPR to target the enzyme NDM-1 which helps bacteria resist a wide range of beta-lactam antibiotics, including carbapenems. Using the technology, they were able to specifically target and destroy over 90 percent of NDM-1 carrying bacteria.
The MIT team also found that they could target antibiotic resistance gene encoding SHV-18, another mutation in the bacterial chromosome that helps bacteria resist quinolone antibiotics. The technology is now being tested in mice with the ultimate goal of adapting CRISPR components to treat infections in human patients.
The second technology being developed against AMR is CombiGEM, a system that enables rapid and systematic search for genetic combinations that increases bacteria’s sensitivity to various antibiotics. The researchers initially compiled a library of 34,000 pairs of bacterial genes, which they delivered into drug-resistant bacteria and treated with different antibiotics. They were able to identify gene combinations that multiplied the destruction of target bacteria by ten thousand to a million-fold. They are now studying how the genes influence antibiotic resistance with the aim of designing new drugs that mimic their effects.
Professor Lu said, “This is a high-throughput technology for uncovering genetic combinations that look really interesting, and then you have to go downstream and figure out the mechanisms… We’re excited about the application of CombiGEM to probe complex multifactorial phenotypes, such as stem cell differentiation, cancer biology, and synthetic circuits.”
The team’s research was funded in part by the National Institutes of Health (NIH).
Last week, the White House announced new measures it will take to maintain the effectiveness of drugs against increasingly resistant bacteria strains. President Obama signed an executive order to authorize a task force to present a potential national strategy against the spread of drug-resistant bacteria. The task force also aims to present a detailed program on how to speed the research and development of antibiotics by 2020.