Bacteria beware: MIT student invents knock-out punch for antibiotic resistance

Delivering a One-Two Punch

Working with his advisor, J.J. Collins, professor of biomedical engineering at Boston University, Lu developed two bacteriophage platforms to overcome antibiotic resistance. Bacteriophage are viruses that only infect bacteria, not human cells. They have been used since the early 20th century to treat bacterial infections; however, they fell out of favor in the United States due to the advent of antibiotics. Lu’s work represents an exciting application of synthetic biology, which is an emerging field focused on the rational engineering of organisms to achieve novel functions.

Lu has engineered bacteriophage to boost antibiotic effectiveness. The bacteriophage carries DNA that codes for factors that target bacterial gene networks, which former treatments failed to reach, and destroys bacterial antibiotic resistance mechanisms. The weakened bacterial defenses enable antibiotics to perform better. Administered together, Lu’s bacteriophage and antibiotics have the potential to eliminate nearly 30,000 times more bacteria than antibiotics alone, including cells that survive antibiotic-only treatment. This combination treatment also thwarts development of stronger antibiotic resistance, which can extend the lifetime of existing and future antibiotic drugs.

“While working at a hospital as part of a graduate course, I saw many patients who contracted new infections due to already-compromised immune systems or equipment that is extremely difficult to keep sterile,” Lu recalled. “Being infected by difficult-to-eradicate bacteria is a traumatic experience for patients and a serious public health issue that needs attention. I thought that there had to be a solution for these infections.”

Penetrating Biofilms

Lu also applied his work with bacteriophage to create a new technique for reducing harmful biofilms, which are slimy layers of bacteria that develop on the surfaces of medical, industrial and food processing equipment and are difficult to penetrate and remove. Current treatment methods to penetrate biofilms can involve peptides or enzymes, which must be administered systemically and are costly. Medical devices infected by biofilms, such as replacement hip joints or pacemakers, often have to be removed surgically.

Lu invented enzymatically-active bacteriophage that directly target the infection site, where they can simultaneously penetrate the biofilm’s protective slime layer and kill the bacteria underneath. “Think of it as a Trojan Horse,” he explained. “First you sneak into the bacteria and use it to overproduce enzymes precisely where they are needed most in order to overwhelm and break up the biofilm slime. Once the slime is disrupted, the bacteriophage then move in and kill the bacteria.”